{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:05:03Z","timestamp":1774519503850,"version":"3.50.1"},"reference-count":387,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instititute of Research Valdecilla (IDIVAL)","award":["NVAL 19\/23"],"award-info":[{"award-number":["NVAL 19\/23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer\u2019s disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways.<\/jats:p>","DOI":"10.3390\/ijms21186906","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"6906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Signalling Pathways Implicated in Alzheimer\u2032s Disease Neurodegeneration in Individuals with and without Down Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-1156","authenticated-orcid":false,"given":"Carmen","family":"Mart\u00ednez-Cu\u00e9","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noem\u00ed","family":"Rueda","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"ref_1","unstructured":"(2020, September 18). Alzheimer\u2019s Association Home Page. Available online: http:\/\/Alzh.org."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/B978-0-444-54299-1.00006-6","article-title":"Neurological phenotypes for Down syndrome across the life span","volume":"197","author":"Lott","year":"2012","journal-title":"Prog. Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tins.2011.11.001","article-title":"Trisomy 21 and early brain development","volume":"35","author":"Haydar","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10519-006-9047-x","article-title":"Neuroanatomy of Down syndrome in vivo: A model of preclinical Alzheimer\u00b4s disease","volume":"36","author":"Teipel","year":"2006","journal-title":"Behav. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.bbadis.2011.10.001","article-title":"Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome","volume":"1822","author":"Cenini","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1742-2094-10-84","article-title":"Down\u2019s syndrome, neuroinflammation, and Alzheimer neuropathogenesis","volume":"10","author":"Wilcock","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1001\/archneurol.2011.535","article-title":"Positron emission tomography and neuropathologic estimates of fibrillar amyloid-\u03b2 in a patient with Down syndrome and Alzheimer disease","volume":"68","author":"Sabbagh","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41591-019-0375-9","article-title":"Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer\u2019s disease","volume":"25","author":"Cafini","year":"2019","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apolipoprotein E in Alzheimer\u2019s disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1038\/nn1564","article-title":"Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function","volume":"8","author":"Chang","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3233\/JAD-2010-100351","article-title":"Systemic mitochondrial dysfunction and the etiology of Alzheimer\u2019s disease and down syndrome dementia","volume":"20","author":"Coskun","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1042\/BJ20140772","article-title":"Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: Overlaps in Down\u2019s syndrome and Alzheimer\u2019s disease brain","volume":"463","author":"Butterfield","year":"2014","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18632\/aging.102328","article-title":"Brain pyrimidine nucleotide synthesys and Alzheimer disease","volume":"11","author":"Pesini","year":"2019","journal-title":"Aging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fncel.2020.00016","article-title":"Cellular senescence in neurodegenerative diseases","volume":"14","author":"Rueda","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/156720506775697098","article-title":"Has the amyloid cascade hypothesis for Alzheimer\u2019s disease been proved?","volume":"3","author":"Hard","year":"2006","journal-title":"Curr. Alzheimer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10738","DOI":"10.1073\/pnas.92.23.10738","article-title":"Amyloid beta peptide potentiates cytokine secretion by interleukin-1 beta-activated human astrocytoma cells","volume":"92","author":"Gitter","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1016\/S0024-3205(97)00936-3","article-title":"Effect of a carboxy-terminal fragment of the Alzheimer\u2019s amyloid precursor protein on expression of proinflammatory cytokines in rat glial cells","volume":"61","author":"Chong","year":"1997","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1523\/JNEUROSCI.18-06-02161.1998","article-title":"Fibrillar beta-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo","volume":"18","author":"Weldon","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1007\/s00702-006-0575-6","article-title":"He significance of neuroinflammation in understanding Alzheimer\u2019s disease","volume":"113","author":"Eikelenboom","year":"2006","journal-title":"J. Neural. Transm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.neuroscience.2007.04.011","article-title":"Beta-amyloid pathology in the entorhinal cortex of rats induces memory deficits: Implications for Alzheimer\u2019s disease","volume":"147","author":"Sipos","year":"2007","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/170276","article-title":"Neuroinflammation in the aging Down syndrome brain; Lessons from Alzheimer\u2019s disease","volume":"51","author":"Wilcock","year":"2012","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ritchie, S.J., Hill, W.D., Marioni., R.E., Davies, G., Hagenaars, S.P., Harris, S.E., Cox, S.R., Taylor, A.M., Corley, J., and Pattie, A. (2019). Polygenic predictors of age-related decline in cognitive ability. Mol. Psychiatry, 1\u201315.","DOI":"10.1101\/375691"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103638","DOI":"10.1016\/j.ridd.2020.103638","article-title":"A multi-level developmental approach to exploring individual differences in Down syndrome: Genes, brain, behaviour, and environment","volume":"104","author":"Thomas","year":"2020","journal-title":"Res. Dev. Disabil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrn2620","article-title":"Apolipoprotein E and its receptors in Alzheimer\u2019s disease: Pathways, pathogenesis and therapy","volume":"10","author":"Bu","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","article-title":"Alzheimer mechanisms and therapeutic strategies","volume":"148","author":"Huang","year":"2012","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1002\/gps.2039","article-title":"Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer\u2019s disease and mortality in persons with Down syndrome","volume":"23","author":"Prasher","year":"2008","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.neurobiolaging.2013.11.019","article-title":"Autophagy in aging and neurodegenerative diseases: Implications for pathogenesis and therapy","volume":"35","author":"Tan","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1471-4159.2007.05075.x","article-title":"Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: Evidence for a functional link between Down syndrome and Alzheimer\u2019s disease","volume":"104","author":"Ryoo","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1074\/jbc.271.7.3488","article-title":"Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII","volume":"271","author":"Kentrup","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1006\/geno.1995.1073","article-title":"Construction of a panel of transgenic mice containing a contiguous 2-Mb set of YAC\/P1 clones from human chromosome 21q22.2","volume":"27","author":"Smith","year":"1995","journal-title":"Genomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/ng0597-28","article-title":"Functional screening of 2Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome","volume":"16","author":"Smith","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1093\/hmg\/10.18.1915","article-title":"Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down\u2019s syndrome","volume":"10","author":"Altafaj","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.nbd.2005.12.006","article-title":"DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects","volume":"22","author":"Ahn","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/hmg\/ddl437","article-title":"The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease","volume":"16","author":"Kimura","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1742-4658.2010.07955.x","article-title":"The role of DYRK1A in neurodegenerative diseases","volume":"278","author":"Wegiel","year":"2011","journal-title":"FEBS J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1471-4159.2010.06769.x","article-title":"Dyrk1A-mediated phosphorylation of Presenilin 1: A functional link between Down syndrome and Alzheimer\u2019s disease","volume":"115","author":"Ryu","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1567205052772713","article-title":"Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer\u2019s disease and tauopathies","volume":"2","author":"Ferrer","year":"2005","journal-title":"Curr. Alzheimer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40401","DOI":"10.1074\/jbc.M111.253971","article-title":"Regulation of RCAN1 protein activity by Dyrk1A protein-mediated phosphorylation","volume":"286","author":"Jung","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1080\/13550280290100978","article-title":"Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer\u2019s disease","volume":"8","author":"Mattson","year":"2002","journal-title":"J. Neurovirol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1248\/bpb.b16-00350","article-title":"Perturbed calcineurin-NFAT signaling is associated with the development of Alzheimer\u2019s disease","volume":"39","author":"Asai","year":"2016","journal-title":"Biol. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1096\/fj.06-7246com","article-title":"Renaming the DSCR1\/Adapt78 gene family as RCAN: Regulators of calcineurin","volume":"21","author":"Davies","year":"2007","journal-title":"FASEB J."},{"key":"ref_45","first-page":"7","article-title":"NFATs and Alzheimer\u2019s Disease","volume":"2","author":"Abdul","year":"2010","journal-title":"Mol. Cell Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"38787","DOI":"10.1074\/jbc.M102829200","article-title":"Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer\u2019s disease","volume":"276","author":"Ermak","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nature04678","article-title":"NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21","volume":"441","author":"Arron","year":"2006","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.freeradbiomed.2017.08.009","article-title":"mTOR in Down syndrome: Role in A\u03b2 and tau neuropathology and transition to Alzheimer disease-like dementia","volume":"114","author":"Tramutola","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1474-9726.2007.00360.x","article-title":"Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling","volume":"7","author":"Cho","year":"2008","journal-title":"Aging Cell."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: Renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.exger.2013.02.025","article-title":"PI3-kinase\/Akt\/mTOR signaling: Impaired on\/off switches in aging, cognitive decline and Alzheimer\u2019s disease","volume":"48","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"77sr1","DOI":"10.1126\/scitranslmed.3002369","article-title":"Alzheimer\u2019s disease: The challenge of the second century","volume":"3","author":"Holtzman","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0169-328X(02)00488-6","article-title":"Up-regulation ofmitogen-activated protein kinases ERK1\/2 andMEK1\/2 is associated with the progression of neurofibrillary degeneration in Alzheimer\u2019s disease","volume":"109","author":"Pei","year":"2002","journal-title":"Mol. Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1111\/j.0953-816X.2004.03365.x","article-title":"Increased MAP kinase activity in Alzheimer\u2019s and Down syndrome but not in schizophrenia human brain","volume":"19","author":"Swatton","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ma, T., Hoeffer, C.A., Capetillo-Zarate, E., Yu, F., Wong, H., Lin, M.T., Tampellini, D., Klann, E., Blitzer, R.D., and Gouras, G.K. (2010). Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer\u2019s disease. PLoS ONE.","DOI":"10.1371\/journal.pone.0012845"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1097\/NEN.0000000000000083","article-title":"mTOR Hyperactivation in down syndrome hippocampus appears early during development","volume":"73","author":"Iyer","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/18715273113126660184","article-title":"The Akt-mTOR pathway in Down\u2019s syndrome: The potential use of rapamycin\/rapalogs for treating cognitive deficits","volume":"13","author":"Casanas","year":"2014","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1471-4159.2004.02949.x","article-title":"Activation of Akt\/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer\u2019s disease pathology","volume":"93","author":"Griffin","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1111\/j.1742-4658.2005.04833.x","article-title":"Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer\u2019s disease brain","volume":"272","author":"Li","year":"2005","journal-title":"FEBS J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1111\/j.1582-4934.2008.00509.x","article-title":"mTOR-dependent signalling in Alzheimer\u2019s disease","volume":"12","author":"Peil","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3233\/JAD-131124","article-title":"Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer\u2019s disease","volume":"38","author":"Sun","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1046\/j.1471-4159.2001.00472.x","article-title":"Effect of the Alzheimer amyloid fragment Abeta(25-35) on Akt\/PKB kinase and survival of PC12 cells","volume":"78","author":"Martin","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1093\/brain\/awf205","article-title":"A beta 17-42 in Alzheimer\u2019s disease activates JNK and caspase-8 leading to neuronal apoptosis","volume":"125","author":"Wei","year":"2002","journal-title":"Brain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.bbadis.2014.04.007","article-title":"Neuropathological role of PI3K\/Akt\/mTOR axis in Down syndrome brain","volume":"1842","author":"Perluigi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/jnr.23011","article-title":"Mammalian target of rapamycin: A valid therapeutic target through the autophagy pathway for Alzheimer\u2019s disease?","volume":"90","author":"Cai","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.2147\/NDT.S75717","article-title":"Activation of mTOR: A culprit of Alzheimer\u2019s disease?","volume":"11","author":"Cai","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13107","DOI":"10.1074\/jbc.M110.100420","article-title":"Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: Effects on cognitive impairments","volume":"285","author":"Caccamo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Di Domenico, F., Head, E., Butterfield, D.A., and Perluigi, M. (2014). Oxidative Stress and Proteostasis Network: Culprit and Casualty of Alzheimer\u2019s-Like Neurodegeneration. Adv. Geriatr., 14.","DOI":"10.1155\/2014\/527518"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.tcb.2010.03.002","article-title":"The Beclin 1\u2013VPS34 complex\u2013at the crossroads of autophagy and beyond","volume":"20","author":"Funderburk","year":"2010","journal-title":"Trends Cell. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1242\/jcs.019265","article-title":"Autophagy, amyloidogenesis and Alzheimer disease","volume":"120","author":"Nixon","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pneurobio.2013.06.002","article-title":"Impaired autophagy and APP processing in Alzheimer\u2019s disease: The potential role of Beclin 1 interactome","volume":"106\u2013107","author":"Salminen","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8924","DOI":"10.1074\/jbc.M110.180638","article-title":"Naturally secreted amyloid-beta increases mammalian target of rapamycin (mTOR) activity via a PRAS40-mediated mechanism","volume":"286","author":"Caccamo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Majumder, S., Richardson, A., Strong, R., and Oddo, S. (2011). Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025416"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1096\/fj.06-7703com","article-title":"Amyloid beta oligomers induce impairment of neuronal insulin receptors","volume":"22","author":"Zhao","year":"2008","journal-title":"FASEB J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pnpbp.2013.12.001","article-title":"GSK3\u03b2, CREB, and BDNF in peripheral blood of patients with Alzheimer\u2019s disease and depression","volume":"50","author":"Buchal","year":"2014","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0166-2236(99)01500-3","article-title":"Is CREB a key to neuronal survival?","volume":"23","author":"Walton","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1046\/j.1471-4159.2001.00495.x","article-title":"CREB DNA binding activity is inhibited by glycogen synthase kinase-3\u03b2 and facilitated by lithium","volume":"78","author":"Grimes","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/abio.1994.1356","article-title":"Use of a synthetic peptide as a selective substrate for glycogen synthase kinase 3","volume":"220","author":"Wang","year":"1994","journal-title":"Anal. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.nbd.2011.09.002","article-title":"Activation of glycogen synthase kinase-3 beta mediates \u03b2-amyloid induced neuritic damage in Alzheimer\u2019s disease","volume":"45","author":"Coma","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17301","DOI":"10.1074\/jbc.M010450200","article-title":"\u03b2-amyloid-(1\u201342) impairs activity-dependent cAMPresponse element-binding protein signaling in neurons at concentrations in which cell survival is not compromised","volume":"276","author":"Tong","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13217","DOI":"10.1073\/pnas.172504199","article-title":"Amyloid \u03b2-peptide inhibition of the PKA\/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling","volume":"99","author":"Vitolo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/j.1471-4159.1992.tb11357.x","article-title":"Adenylyl cyclase activity in postmortem human brain: Evidence of altered G protein mediation in Alzheimer\u2019s disease","volume":"58","author":"Cowburn","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0006-8993(94)91692-6","article-title":"Adenylyl cyclase activity in Alzheimer\u2019s disease brain: Stimulatory and inhibitory signal transduction pathways are differently affected","volume":"644","author":"Schnecko","year":"1994","journal-title":"Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2006.06.046","article-title":"Ubiquitin hydrolase Uch-L1 rescues \u03b2-amyloid-induced decreases in synaptic function and contextual memory","volume":"126","author":"Gong","year":"2006","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"16877","DOI":"10.1073\/pnas.0908706106","article-title":"Reversal of long-term dendritic spine alterations in Alzheimer disease models","volume":"106","author":"Smith","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1016\/j.neurobiolaging.2015.04.014","article-title":"CREB expression mediates amyloid \u03b2-induced basal BDNF downregulation","volume":"36","author":"Rosa","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0169-328X(97)00125-3","article-title":"Brain-derived neurotrophic factor is reduced in Alzheimer\u2019s disease","volume":"49","author":"Connor","year":"1997","journal-title":"Mol. Brain Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/archneur.57.6.846","article-title":"Region-specific neurotrophin imbalances in Alzheimer disease: Decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas","volume":"57","author":"Hock","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.brainres.2008.10.055","article-title":"The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival","volume":"1249","author":"Lee","year":"2009","journal-title":"Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"12","DOI":"10.2174\/1874467211003010012","article-title":"Brain-derived neurotrophic factor: A dynamic gatekeeper of neural plasticity","volume":"3","author":"Cowansage","year":"2010","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"627","DOI":"10.2217\/fnl.11.44","article-title":"Brain-derived neurotrophic factor: The link between amyloid-\u03b2 and memory loss","volume":"6","author":"Fahnestock","year":"2011","journal-title":"Future Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/j.1471-4159.2005.03135.x","article-title":"Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer\u2019s disease","volume":"93","author":"Peng","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1523\/JNEUROSCI.5053-06.2007","article-title":"Oligomeric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells","volume":"27","author":"Garzon","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"134541","DOI":"10.1016\/j.neulet.2019.134541","article-title":"microRNAs expression correlates with levels of APP, DYRK1A, hyperphosphorylated Tau and BDNF in the hippocampus of a mouse model for Down syndrome during ageing","volume":"714","author":"Chaves","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_96","first-page":"16","article-title":"Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down\u2019s syndrome","volume":"82","author":"Benito","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"331","DOI":"10.14336\/AD.2015.0825","article-title":"The involvement of BDNF, NGF and GDNF in aging and Alzheimer\u2019s disease","volume":"6","author":"Budni","year":"2015","journal-title":"Aging Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1097\/NEN.0b013e3181c22569","article-title":"Increased matrix metalloproteinase 9 activity in mild cognitive impairment","volume":"68","author":"Bruno","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/brain\/awt372","article-title":"Nerve growth factor metabolic dysfunction in Down\u2019s syndrome brains","volume":"137","author":"Iulita","year":"2014","journal-title":"Brain"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"13139","DOI":"10.1073\/pnas.0806133105","article-title":"NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons","volume":"105","author":"Matrone","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9402","DOI":"10.1523\/JNEUROSCI.2154-10.2010","article-title":"Amyloid disrupts activity-dependent gene transcription required for memory through the CREB coactivator CRTC1","volume":"30","author":"Valero","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1750-1326-6-60","article-title":"Downregulation of CREB expression in Alzheimer\u2019s brain and in A\u03b2-treated rat hippocampal neurons","volume":"6","author":"Pugazhenthi","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2174\/157015911798376190","article-title":"The neurotrophins and their role in Alzheimer\u2019s disease","volume":"9","author":"Allen","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1101\/lm.54603","article-title":"BDNF and activity-dependent synaptic modulation","volume":"10","author":"Lu","year":"2003","journal-title":"Learn. Mem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1523\/JNEUROSCI.21-12-04125.2001","article-title":"\u03b2-Amyloid activates the mitogenactivated protein kinase cascade via hippocampal \u03b17 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer\u2019s disease","volume":"21","author":"Dineley","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"22768","DOI":"10.1074\/jbc.M200164200","article-title":"Accelerated plaque accumulation, associative learning deficits, and up-regulation of \u03b17 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins","volume":"277","author":"Dineley","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1172\/JCI22831","article-title":"Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment","volume":"114","author":"Gong","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0006-8993(91)90681-K","article-title":"Abnormal phosphorylation of tau precedes ubiquitination in neurofibrillary pathology of Alzheimer disease","volume":"539","author":"Bancher","year":"1991","journal-title":"Brain Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.1073\/pnas.83.13.4913","article-title":"Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology","volume":"83","author":"Iqbal","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1042\/bj2750099","article-title":"Tau in Alzheimer\u2019s disease and Down\u2019s syndrome is insoluble and abnormally phosphorylated","volume":"275","author":"Hanger","year":"1991","journal-title":"Biochem. J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.arcmed.2012.10.012","article-title":"Role of tau protein in neuronal damage in Alzheimer\u2019s disease and Down syndrome","volume":"43","author":"Cardenas","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0006-8993(92)91476-U","article-title":"Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments","volume":"597","author":"Liu","year":"1992","journal-title":"Brain Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1038\/sj.emboj.7601917","article-title":"Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau","volume":"26","author":"Kimura","year":"2007","journal-title":"EMBO J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1093\/jnen\/62.9.917","article-title":"Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome","volume":"62","author":"Head","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1096\/fj.07-104539","article-title":"Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome","volume":"22","author":"Liu","year":"2008","journal-title":"FASEB J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1093\/hmg\/ddl211","article-title":"Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome","volume":"15","author":"Shukkur","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1042\/bj3550609","article-title":"The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: Potential role for DYRK as a glycogen synthase kinase 3-priming kinase","volume":"355","author":"Woods","year":"2001","journal-title":"Biochem. J."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Azorsa, D.O., Robeson, R.H., Frost, D., Meec Hoovet, B., Brautigam, G.R., Dickey, C., Beaudry, C., Basu, G.D., Holz, D.R., and Hernandez, J.A. (2010). High-content siRNA screening of the kinome identifies kinases involved in Alzheimer\u2019s disease-related tau hyperphosphorylation. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-25"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Frost, D., Meechoovet, B., Wang, T., Gately, S., Giorgetti, M., Shcherbakova, I., and Dunckley, T. (2011). beta-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer\u2019s disease-related sites. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019264"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"30497","DOI":"10.1074\/jbc.M112.355412","article-title":"Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine\/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion","volume":"287","author":"Yin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/nrc2735","article-title":"NFAT proteins: Emerging roles in cancer progression","volume":"9","author":"Mancini","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.tcb.2007.04.006","article-title":"NFAT signaling and the invention of vertebrates","volume":"17","author":"Wu","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","article-title":"Multiple isoforms of humanmicrotubule-associated protein tau: Sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease","volume":"3","author":"Goedert","year":"1989","journal-title":"Neuron"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"28660","DOI":"10.1074\/jbc.M802645200","article-title":"Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome","volume":"283","author":"Shi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/NEN.0b013e318202bfa1","article-title":"Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome","volume":"70","author":"Wegiel","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1096\/fj.11-185728","article-title":"Do RCAN1 proteins link chronic stress with neurodegeneration?","volume":"25","author":"Ermak","year":"2011","journal-title":"FASEB J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1042\/BJ20060463","article-title":"Phosphorylation inhibits turnover of the tau protein by the proteasome: Influence of RCAN1 and oxidative stress","volume":"400","author":"Poppek","year":"2006","journal-title":"Biochem. J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3233\/JAD-2011-110890","article-title":"Amyloid-beta toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer\u2019s Disease","volume":"27","author":"Lloret","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1111\/j.1742-4658.2006.05217.x","article-title":"RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3beta","volume":"273","author":"Ermak","year":"2006","journal-title":"FEBS J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1046\/j.1471-4159.2000.0741587.x","article-title":"Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: Differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun Nterminal kinase and P38, and glycogen synthase kinase-3b","volume":"74","author":"Reynolds","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0168-0102(98)00061-3","article-title":"Activation of tau protein kinaseI\/glycogen synthase kinase-3beta by amyloid beta peptide enhances phosphorylation of tau in hippocampal neurons","volume":"31","author":"Takashima","year":"1998","journal-title":"Neurosci. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1084\/jem.20081588","article-title":"Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer\u2019s disease mouse models","volume":"205","author":"Qing","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neuroscience.2008.07.025","article-title":"Abnormal expression of synaptic proteins and neurotrophin-3 in the Down syndrome mouse model Ts65Dn","volume":"156","author":"Pollonini","year":"2008","journal-title":"Neuroscience"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0896-6273(03)00627-5","article-title":"Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles","volume":"40","author":"Cruz","year":"2003","journal-title":"Neuron"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1021\/bi051635j","article-title":"Cyclindependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3b","volume":"45","author":"Li","year":"2006","journal-title":"Biochemistry"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3233\/JAD-2008-13307","article-title":"Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome","volume":"13","author":"Liang","year":"2008","journal-title":"J. Alzheimers Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fnmol.2014.00016","article-title":"Protein phosphatase 2A dysfunction in Alzheimer\u2019s disease","volume":"7","author":"Sontag","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1016\/j.febslet.2006.06.021","article-title":"Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine","volume":"580","author":"Chohan","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1111\/j.1460-9568.2005.04391.x","article-title":"Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation","volume":"22","author":"Liu","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1471-4159.1993.tb03603.x","article-title":"Phosphoprotein phosphatase-Activities in alzheimer-disease brain","volume":"61","author":"Gong","year":"1993","journal-title":"J. Neurochem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1046\/j.1471-4159.1995.65020732.x","article-title":"Phosphataseactivity toward abnormally phosphorylated-tau - decrease in alzheimer-disease brain","volume":"65","author":"Gong","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0306-4522(02)00697-8","article-title":"Inhibition of protein phosphatase 2A- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats","volume":"118","author":"Sun","year":"2003","journal-title":"Neuroscience"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/NEN.0b013e3181922348","article-title":"Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease","volume":"68","author":"Julien","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3233\/JAD-151105","article-title":"Activation of p53 in Down Syndrome and in the Ts65Dn Mouse Brain is Associated with a Pro-Apoptotic Phenotype","volume":"52","author":"Tramutola","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"13223","DOI":"10.1074\/jbc.M110.102574","article-title":"DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1","volume":"285","author":"Guo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/jnen\/64.4.263","article-title":"The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease","volume":"64","author":"Counts","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1212\/01.wnl.0000256373.39415.b1","article-title":"Cortical biochemistry in MCI and Alzheimer disease: Lack of correlation with clinical diagnosis","volume":"68","author":"Forman","year":"2007","journal-title":"Neurology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.nurx.2006.05.007","article-title":"Single cell gene expression profiling in Alzheimer\u2019s disease","volume":"3","author":"Ginsberg","year":"2006","journal-title":"NeuroRx"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1111\/j.1471-4159.2005.03641.x","article-title":"Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer\u2019s disease","volume":"96","author":"Ginsberg","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1101\/lm.69204","article-title":"The cholinergic lesion of Alzheimer\u02c7\u0131s disease: Pivotal factor or side show","volume":"11","author":"Mesulam","year":"2004","journal-title":"Learn. Mem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/NEN.0b013e31816a1df3","article-title":"Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease","volume":"67","author":"Geula","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s004019900178","article-title":"Evolution of Alzheimer\u2019s disease-related cytoskeletal changes in the basal nucleus of Meynert","volume":"100","author":"Sassin","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"152","DOI":"10.2174\/156720509787602843","article-title":"Early Tau pathology involving the septo-hippocampal pathway in a Tau transgenic model: Relevance to Alzheimer\u2019s disease","volume":"6","author":"Belarbi","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1046\/j.1471-4159.2000.740777.x","article-title":"Increased levels of tau protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists","volume":"74","author":"Moore","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1124\/pr.108.000562","article-title":"Nicotinic acetylcholine receptor signaling: Roles in Alzheimer\u2019s disease and amyloid neuroprotection","volume":"61","author":"Buckingham","year":"2009","journal-title":"Pharm. Rev."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.mehy.2009.09.011","article-title":"Alpha7 neuronal nicotinic receptors: The missing link to understanding Alzheimer\u2019s etiopathology?","volume":"74","author":"Bencherif","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"31547","DOI":"10.1074\/jbc.M212532200","article-title":"\u03b17 nicotinic acetylcholine receptors mediate \u03b2-amyloid peptide-induced tau protein phosphorylation","volume":"278","author":"Wang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.neuron.2006.01.020","article-title":"M1 receptors play a central role in modulating AD-like pathology in transgenic mice","volume":"49","author":"Caccamo","year":"2006","journal-title":"Neuron"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the cholinergic system","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/brain\/awh671","article-title":"Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation \u2013 a pharmacological fMRI study","volume":"129","author":"Goekoop","year":"2006","journal-title":"Brain"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1046\/j.1471-4159.1995.64020749.x","article-title":"Neurochemical correlates of dementia severity in Alzheimer\u2019s disease: Relative importance of the cholinergic deficits","volume":"64","author":"Bierer","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2174\/1381612043386473","article-title":"Functional neurochemistry of Alzheimer\u2019s disease","volume":"10","author":"Gsell","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s11064-007-9497-4","article-title":"The place of choline acetyltransferase activity measurement in the \u201ccholinergic hypothesis\u201d of neurodegenerative diseases","volume":"33","author":"Contestabile","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1586\/14737175.8.11.1703","article-title":"Cholinergic system during the progression of Alzheimer\u2019s disease: Therapeutic implications","volume":"8","author":"Mufson","year":"2008","journal-title":"Exp. Rev. Neurother."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0169-328X(00)00031-0","article-title":"Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients","volume":"76","author":"Burghaus","year":"2000","journal-title":"Mol. Brain Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0306-4522(03)00460-3","article-title":"Protein and mRNA levels of nicotinic receptors in brain of tobacco using controls and patients with Alzheimer\u2019s disease","volume":"122","author":"Mousavi","year":"2003","journal-title":"Neuroscience"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0006-3223(00)01125-2","article-title":"Nicotinic receptor abnormalities of Alzheimer\u2019s disease: Therapeutic implications","volume":"49","author":"Nordberg","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0022-510X(82)90045-4","article-title":"Alzheimer\u2019s disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities","volume":"57","author":"Wilcock","year":"1982","journal-title":"J. Neurol. Sci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0306-4522(94)00410-7","article-title":"Alteration in nicotine binding sites in Parkinson\u2019s disease. Lewy body dementia and Alzheimer\u2019s disease: Possible index of early neuropathology","volume":"64","author":"Perry","year":"1995","journal-title":"Neuroscience"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/156720507781788855","article-title":"Cholinotrophic molecular substrates of mild cognitive impairment in the elderly","volume":"4","author":"Mufson","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2174\/156720507781788774","article-title":"NGF-cholinergic dependency in brain aging. MCI and Alzheimer\u2019s disease","volume":"4","author":"Cuello","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0301-0082(02)00079-5","article-title":"Alzheimer\u2019s disease and the basal forebrain cholinergic system: Relations to \u03b2-amyloid peptides, cognition, and treatment strategies","volume":"68","author":"Auld","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2174\/1567205043331992","article-title":"Alzheimer\u2019s disease: Interactions between cholinergic functions and \u03b2-amyloid","volume":"1","author":"Yan","year":"2004","journal-title":"Curr. Alzheimer Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0006-8993(02)03262-6","article-title":"Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish mutation of human beta-amyloid precursor protein","volume":"953","author":"Apelt","year":"2002","journal-title":"Brain Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.freeradbiomed.2016.10.490","article-title":"Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of alzheimer disease and other selected age-related neurodegenerative disorders","volume":"111","author":"Tramutola","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Rueda, N., and Mart\u00ednez-Cu\u00e9, C. (2020). Antioxidants in Down Syndrome: From Preclinical Studies to Clinical Trials. Antioxidants, 9.","DOI":"10.3390\/antiox9080692"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/jnc.14589","article-title":"Redox proteomics and amyloid \u03b2-peptide: Insights into Alzheimer disease","volume":"151","author":"Butterfield","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.3109\/10715762.2012.714466","article-title":"Are oxidative stress and mitochondrial dysfunction the key players in the neurodegenerative diseases?","volume":"46","author":"Giacomazza","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.bbadis.2011.12.010","article-title":"Antioxidants in Down syndrome","volume":"1822","author":"Lott","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Perluigi, M., and Butterfield, D.A. (2012). Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia. Curr. Gerontol. Geriatr. Res., 724904.","DOI":"10.1155\/2012\/724904"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrn3983","article-title":"A genetic cause of Alzheimer disease: Mechanistic insights from Down syndrome","volume":"16","author":"Wiseman","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_182","first-page":"1281","article-title":"Cu\/Zn-superoxide dismutase and glutathione peroxidase during aging","volume":"35","author":"Cristiano","year":"1995","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"14088","DOI":"10.1074\/jbc.M111.305342","article-title":"Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells","volume":"287","author":"Ermak","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Sun, X., Wu, Y., Herculano, B., and Song, W. (2014). RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095471"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3858\/emm.2009.41.7.052","article-title":"Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin","volume":"41","author":"Lee","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.nbd.2006.12.022","article-title":"Beta-amyloid causes downregulation of calcineurin in neurons through induction of oxidative stress","volume":"26","author":"Celsi","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1006\/abbi.1997.0109","article-title":"Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress","volume":"342","author":"Crawford","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.3233\/JAD-170543","article-title":"Oxidative stress, amyloid-b peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer\u2019s disease","volume":"62","author":"Butterfield","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_189","first-page":"S47","article-title":"Excitotoxicity: An overview","volume":"16","author":"Olney","year":"1990","journal-title":"Can. Dis. Wkly. Rep."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2165\/00023210-200317090-00004","article-title":"The glutamatergic system and Alzheimer\u2019s disease: Therapeutic implications","volume":"17","author":"Butterfield","year":"2003","journal-title":"CNS Drugs"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0891-5849(02)00794-3","article-title":"Lipid peroxidation and protein oxidation in Alzheimer\u2019s disease brain: Potential causes and consequences involving amyloid b-peptide-associated free radical oxidative stress","volume":"32","author":"Butterfield","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/ars.2016.6759","article-title":"The triangle of death in Alzheimer\u2019s disease brain: The aberrant cross-talk among energy metabolism, mammalian target of rapamycin signaling, and protein homeostasis revealed by redox proteomics","volume":"26","author":"Barone","year":"2017","journal-title":"Antioxid. Redox Signal"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"101162","DOI":"10.1016\/j.redox.2019.101162","article-title":"Restoration of aberrant mTOR signaling by intranasal rapamycing reduces oxidative damage: Focus on HNE-modified proteins in a mouse model of Down syndrome","volume":"23","author":"Tramutola","year":"2019","journal-title":"Redox Biol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.bbadis.2013.04.013","article-title":"Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer\u2019s disease neuropathology: Redox proteomics analysis of human brain","volume":"1832","author":"Coccia","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.freeradbiomed.2014.03.027","article-title":"Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: Clues for understanding the development of Alzheimer disease","volume":"71","author":"Pupo","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000441419","article-title":"Increased Mammalian Target of Rapamycin Signaling Contributes to the Accumulation of Protein Oxidative Damage in a Mouse Model of Down\u2019s Syndrome","volume":"16","author":"Tramutola","year":"2016","journal-title":"Neurodegener. Dis."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.nbd.2015.03.014","article-title":"mTOR signaling in aging and neurodegeneration: At the crossroad between metabolism dysfunction and impairment of autophagy","volume":"84","author":"Perluigi","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40035-018-0133-9","article-title":"Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome","volume":"7","author":"Tramutola","year":"2018","journal-title":"Transl. Neurodegener."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1478-811X-12-23","article-title":"Signaling pathway cross talk in Alzheimer\u2019s disease","volume":"12","author":"Godoy","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1474-9726.2007.00294.x","article-title":"Oxidative stress and aberrant signaling in aging and cognitive decline","volume":"6","author":"Schipper","year":"2007","journal-title":"Aging Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2046-2395-3-7","article-title":"The role of mitochondria in longevity and healthspan","volume":"3","author":"Brand","year":"2014","journal-title":"Longev. Healthspan"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"8940","DOI":"10.1523\/JNEUROSCI.0026-12.2012","article-title":"Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing","volume":"32","author":"Hall","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mehy.2003.12.045","article-title":"A \u201cmitochondrial cascade hypothesis\u201d for sporadic Alzheimer\u2019s disease","volume":"63","author":"Swerdlow","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainresbull.2016.08.009","article-title":"Amyloid precursor protein processing and bioenergetics","volume":"133","author":"Wilkins","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3233\/JAD-140384","article-title":"OXPHOS, pyrimidine nucleotides, and Alzheimer\u2019s disease: A pharmacogenomics approach","volume":"42","author":"Pesini","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_207","first-page":"211","article-title":"Differential display reveals deteriorated mRNA levels of NADH3 (complex I) in cerebellum of patients with Down syndrome","volume":"57","author":"Krapfenbauer","year":"1999","journal-title":"J. Neural. Transm. Suppl."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1080\/14767058.2016.1262343","article-title":"A polymorphism (rs1042522) in TP53 gene is a risk factor for Down Syndrome in Sicilian mothers","volume":"30","author":"Salemi","year":"2017","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Conti, A., Fabbrini, F., D\u2019Agostino, P., Negri, R., Greco, D., Genesio, R., D\u2019Armiento, M., Olla, C., Paladini, D., and Zannini, M. (2007). Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy. BMC Genom., 8.","DOI":"10.1186\/1471-2164-8-268"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/hmg\/dds529","article-title":"Chronic pro-oxidative state and mitocondrial dysfunctions are more pronounced in fibroblasts from Down syndrome foeti with congenital heart defects","volume":"22","author":"Piccoli","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biocel.2017.09.017","article-title":"Dysfunctions of mitochondria in close association with strong perturbation of long noncoding RNAs expression in Down syndrome","volume":"92","author":"Qiu","year":"2017","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1007\/PL00000661","article-title":"Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer\u2019s disease and Down syndrome","volume":"57","author":"Kim","year":"2000","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_213","first-page":"273","article-title":"Increased protein levels of heterogeneous nuclear ribonucleoprotein A2\/B1 in fetal Down syndrome brains","volume":"57","author":"Kim","year":"2001","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1016\/S0024-3205(01)01074-8","article-title":"The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer\u2019s disease","volume":"68","author":"Kim","year":"2001","journal-title":"Life Sci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/BJ20100581","article-title":"Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy","volume":"431","author":"Valenti","year":"2010","journal-title":"Biochem. J."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1042\/BJ20101908","article-title":"Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: Involvement of the cAMP\/PKA signalling pathway","volume":"435","author":"Valenti","year":"2011","journal-title":"Biochem. J."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.bbadis.2012.12.011","article-title":"Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down\u2019s syndrome","volume":"1832","author":"Valenti","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_218","first-page":"1056","article-title":"Metformin restores the mitochondrial network and reverses mitochondrial dysfunction in Down syndrome cells","volume":"26","author":"Izzo","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"18769","DOI":"10.1073\/pnas.1911895116","article-title":"Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome","volume":"116","author":"Panagaki","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cmet.2012.12.005","article-title":"Adaptive downregulation of mitochondrial function in Down syndrome","volume":"17","author":"Helguera","year":"2013","journal-title":"Cell Metab."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s10020-018-0004-y","article-title":"Mitochondrial dysfunction in down syndrome: Molecular mechanisms and therapeutic targets","volume":"24","author":"Izzo","year":"2018","journal-title":"Mol. Med."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1093\/hmg\/ddu157","article-title":"NRIP1\/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome","volume":"23","author":"Izzo","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1515\/BC.2006.170","article-title":"Mitochondrial signaling, TOR, and life span","volume":"387","author":"Schieke","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex","volume":"307","author":"Sarbassov","year":"2005","journal-title":"Science"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nut.2010.07.021","article-title":"Brain fuel metabolism, aging, and Alzheimer\u2019s disease","volume":"27","author":"Cunnane","year":"2011","journal-title":"Nutrition"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"e426","DOI":"10.1111\/j.1467-789X.2010.00825.x","article-title":"Body mass index in midlife and late-life as a risk factor for dementia: A metaanalysis of prospective studies","volume":"12","author":"Anstey","year":"2011","journal-title":"Obes. Rev."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1159\/000330020","article-title":"Vascular risk factors and dementia: 40-year follow-up of a population-based cohort","volume":"31","author":"Ronnemaa","year":"2011","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"E51","DOI":"10.1002\/oby.20037","article-title":"Midlife obesity and dementia: Metaanalysis and adjusted forecast of dementia prevalence in the United States and China","volume":"21","author":"Loef","year":"2013","journal-title":"Obesity"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association between midlife vascular risk factors and estimated brain amyloid deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Hayden, M.R. (2019). Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer\u2019s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy. Brain Sci., 9.","DOI":"10.20944\/preprints201907.0265.v2"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3389\/fnins.2018.00383","article-title":"Alzheimer\u2019s disease and type 2 diabetes: A critical assessment of the shared pathological traits","volume":"12","author":"Chatterjee","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Tumminia, A., Vinciguerra, F., Parisi, M., and Frittitta, L. (2018). Type 2 diabetes mellitus and Alzheimer\u2019s disease: Role of insulin signalling and therapeutic implications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113306"},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Tang, B.L. (2020). Glucose, glycolysis, and neurodegenerative diseases. J. Cell. Physiol., 1\u201310.","DOI":"10.1002\/jcp.29682"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000231980","article-title":"Midlife serum cholesterol and increased risk of Alzheimer\u2019s and vascular dementia three decades later","volume":"28","author":"Soloman","year":"2009","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.3233\/JAD-140954","article-title":"Midlife vascular risk factors and the risk of Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"42","author":"Meng","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"229","DOI":"10.7762\/cnr.2018.7.4.229","article-title":"Diabetes and Alzheimer\u2019s disease: Mechanisms and nutritional aspects","volume":"7","author":"Lee","year":"2018","journal-title":"Clin. Nutr. Res."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3233\/JAD-161250","article-title":"Type 1 diabetes mellitus and cognitive impairments: A systematic review","volume":"57","author":"Li","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3233\/JAD-140018","article-title":"The pancreas-brain axis: Insight into disrupted mechanisms associating type 2 diabetes and Alzheimer\u2019s disease","volume":"42","author":"Desai","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"104772","DOI":"10.1016\/j.nbd.2020.104772","article-title":"Brain insulin resistance triggers early onset Alzheimer disease in Dowon syndrome","volume":"137","author":"Tramutola","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrn4019","article-title":"Hippocampal insulin resistance and cognitive dysfunction","volume":"16","author":"Biessels","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1172\/JCI64595","article-title":"Alzheimer\u2019s disease and insulin resistance: Translating basic science into clinical applications","volume":"123","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/jnc.13037","article-title":"Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): Analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD","volume":"133","author":"Tramutola","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_244","first-page":"161","article-title":"Insulin in the brain: Its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer\u2019s disease","volume":"5","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/ana.410350507","article-title":"Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer\u2019s disease","volume":"35","author":"Simpson","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"871","DOI":"10.3389\/fnins.2019.00871","article-title":"Reduction of glycolysis intermediate concentrations in the cerebrospinal fluid of Alzheimer\u2019s disease patients","volume":"13","author":"Bergau","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.exger.2017.07.004","article-title":"A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer\u2019s disease","volume":"107","author":"Croteau","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"e12924","DOI":"10.1111\/acel.12924","article-title":"Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer\u2019s disease neurons","volume":"18","author":"Theurey","year":"2019","journal-title":"Aging Cell"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1136\/jnnp.62.6.596","article-title":"Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer\u2019s disease as shown by MRI and PET","volume":"62","author":"Yamaguchi","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.arr.2016.02.003","article-title":"Brain fluordeoxyglucose (FDG) PET in dementia","volume":"30","author":"Kato","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fnint.2017.00018","article-title":"Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, requiring glutamate","volume":"11","author":"Hertz","year":"2017","journal-title":"Front. Integr Neurosci."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","article-title":"Sugar for the brain: The role of glucose in physiological and pathological brain function","volume":"36","author":"Mergenthaler","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s00125-004-1662-6","article-title":"Regulation of insulin signalling by hyperinsulinaemia: Role of IRS-1\/2 serine phosphorylation and the mTOR\/p70 S6K pathway","volume":"48","author":"Ueno","year":"2005","journal-title":"Diabetologia"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/jcp.24351","article-title":"mTOR signaling for biological control and cancer","volume":"228","author":"Alayev","year":"2013","journal-title":"J. Cell Physiol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell. Biol."},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Spilman, P., Podlutskaya, N., Hart, M.J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., and Galvan, V. (2010). Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer\u2019s disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009979"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000129697","article-title":"Senescence, apoptosis or autophagy? When a damaged cell must decide its path-a mini-review","volume":"54","author":"Vicencio","year":"2008","journal-title":"Gerontology"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.12688\/f1000research.10903.1","article-title":"Senescence in the aging process","volume":"6","author":"Faragher","year":"2017","journal-title":"F1000Res"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1128\/MCB.19.3.2109","article-title":"Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts","volume":"19","author":"Stein","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.molcel.2014.05.007","article-title":"Transient activation of p53 in G2 phase is sufficient to induce senescence","volume":"55","author":"Krenning","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.18632\/aging.100971","article-title":"Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses","volume":"8","author":"Alessio","year":"2016","journal-title":"Aging"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.bbabio.2015.05.017","article-title":"Mitochondria: Are they causal players in cellular senescence?","volume":"1847","author":"Passos","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000484629","article-title":"mTOR as regulator of lifespan, aging, and cellular senescence: A mini-review","volume":"64","author":"Weichhart","year":"2018","journal-title":"Gerontology"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-8935-1-6","article-title":"Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence","volume":"1","author":"Nakamura","year":"2008","journal-title":"Epigenetics Chromatin"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1091\/mbc.e11-10-0884","article-title":"Lamin B1 loss is a senescence-associated biomarker","volume":"23","author":"Freund","year":"2012","journal-title":"Mol. Biol. Cell."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mad.2017.08.003","article-title":"The ATF6 arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2\/prostaglandin E2 intracrine pathway","volume":"170","author":"Cormenier","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41593-019-0372-9","article-title":"Senolytic therapy alleviates A\u03b2-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer\u2019s disease model","volume":"22","author":"Zhang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"e12840","DOI":"10.1111\/acel.12840","article-title":"Tau protein aggregation is associated with cellular senescence in the brain","volume":"17","author":"Musi","year":"2018","journal-title":"Aging Cell."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1055\/s-0032-1314892","article-title":"Cytokine and chemokine alterations in Down syndrome","volume":"29","author":"Roberson","year":"2012","journal-title":"Am. J. Perinatol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.bbi.2018.05.008","article-title":"Anti-IL17 treatment ameliorates Down syndrome phenotypes in mice","volume":"73","author":"Rueda","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13041-019-0535-3","article-title":"Transcriptional activation of UPS16 gene expression by NFkB signaling","volume":"12","author":"Yang","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature12530","article-title":"Usp16 contributes to somatic stem-cell defects in Down\u2019s syndrome","volume":"501","author":"Adorno","year":"2013","journal-title":"Nature"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"17506","DOI":"10.1038\/s41598-018-34562-w","article-title":"Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation","volume":"8","author":"Adorno","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1667\/RR14407.1","article-title":"Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks","volume":"185","author":"Wang","year":"2016","journal-title":"Radiat Res."},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Olivieri, F., Prattichizzo, F., Grillari, J., and Balistreri, C.R. (2018). Cellular senescence and inflammaging in age-related diseases. Med. Inflamm., 9076485.","DOI":"10.1155\/2018\/9076485"},{"key":"ref_276","doi-asserted-by":"crossref","unstructured":"Fuster-Matanzo, A., Llorens-Mart\u00edn, M., Hern\u00e1ndez, F., and Avila, J. (2013). Role of neuroinflammation in adult neurogenesis and Alzheimer disease: Therapeutic approaches. Mediat. Inflamm., 260925.","DOI":"10.1155\/2013\/260925"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2013.10.004","article-title":"Neuroinflammation: The role and consequences","volume":"79","author":"Lyman","year":"2014","journal-title":"Neurosci. Res."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2013.10.037","article-title":"Snapshot: Genetics of Alzheimer\u2019s disease","volume":"155","author":"Guerreiro","year":"2013","journal-title":"Cell"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/brain\/awv395","article-title":"Immunosenescence of microglia and macrophages: Impact on the ageing central nervous system","volume":"139","author":"Rawji","year":"2016","journal-title":"Brain"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0014-5793(91)80737-N","article-title":"Interleukin-6 and \u03b1-2-macroglobulin indicate an acute-phase state in Alzheimer\u2019s disease cortices","volume":"285","author":"Bauer","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/BF00571510","article-title":"Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer\u2019s disease patients","volume":"89","author":"Huell","year":"1995","journal-title":"Acta Neuropathol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0014-4886(03)00180-8","article-title":"P38 MAP kinase is activated at early stages in Alzheimer\u2019s disease brain","volume":"183","author":"Sun","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1136\/jnnp-2017-316201","article-title":"Peripheral inflammatory markers in Alzheimer\u2019s disease: A systematic review and meta-analysis of 175 studies","volume":"88","author":"Lai","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3389\/fimmu.2018.00586","article-title":"Age and age-related diseases: Role of inflammation triggers and cytokines","volume":"9","author":"Rea","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2174\/156720506779025242","article-title":"Pathways by which A\u03b2 facilitates tau pathology","volume":"3","author":"Laferla","year":"2006","journal-title":"Curr. Alzheimer Res."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/jnc.13411","article-title":"The contribution of neuroinflammation to amyloid toxicity in Alzheimer\u2019s disease","volume":"136","author":"Minter","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/42257","article-title":"Microglial activation by alzhelmer amyloid precursor protein and modulation by apolipoprotein E","volume":"388","author":"Barger","year":"1997","journal-title":"Nature"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2174\/1568010053586237","article-title":"Mechanisms of cell signaling and inflammation in Alzheimer\u2019s disease","volume":"4","author":"Ho","year":"2004","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"9796","DOI":"10.1523\/JNEUROSCI.23-30-09796.2003","article-title":"Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-\u03b3 agonists modulate immunostimulated processing of amyloid precursor protein through regulation of \u03b2-secretase","volume":"23","author":"Sastre","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1073\/pnas.0503839103","article-title":"Nonsteroidal anti-inflammatory drugs repress \u03b2- secretase gene promoter activity by the activation of PPARgamma","volume":"103","author":"Sastre","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3233\/JAD-2005-8406","article-title":"Potential inflammatory biomarkers in Alzheimer\u2019s disease","volume":"8","author":"Mrak","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","article-title":"Inflammation and Alzheimer\u2019s disease","volume":"21","author":"Akiyama","year":"2000","journal-title":"Neurobiol. Aging"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1523\/JNEUROSCI.06-08-02240.1986","article-title":"Glucocorticoid toxicity in the hippocampus: Reversal by supplementation with brain fuels","volume":"6","author":"Sapolsky","year":"1986","journal-title":"J. Neurosci."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1152\/ajpendo.00453.2006","article-title":"Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism","volume":"292","author":"Qi","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0197-4580(01)00299-8","article-title":"Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice","volume":"22","author":"Lim","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ebiom.2018.11.026","article-title":"Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders","volume":"38","author":"Vogel","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1172\/JCI97229","article-title":"Microglia are required for protection against lethal coronavirus encephalitis in mice","volume":"128","author":"Wheeler","year":"2018","journal-title":"J. Clin. Invest."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ni.1636","article-title":"The NALP3 inflammasome is involved in the innate immune response to amyloid-beta","volume":"9","author":"Halle","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1172\/JCI77487","article-title":"Prostaglandin signaling suppresses beneficial microglial function in Alzheimer\u2019s disease models","volume":"125","author":"Johansson","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1093\/brain\/awh531","article-title":"LPS receptor (CD14): A receptor for phagocytosis of Alzheimer\u2019s amyloid peptide","volume":"128","author":"Liu","year":"2005","journal-title":"Brain"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/acel.12522","article-title":"Distinct inflammatory phenotypes of microglia and monocyte-derived macrophages in Alzheimer\u2019s disease models: Effects of aging and amyloid pathology","volume":"16","author":"Martin","year":"2017","journal-title":"Aging Cell"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00401-018-01957-y","article-title":"Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo","volume":"137","author":"Stancu","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fnagi.2020.00110","article-title":"Microglia and Wnt pathways: Prospects for inflammation in Alzheimer\u2019s disease","volume":"12","author":"Yang","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/hipo.20308","article-title":"Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice","volume":"17","author":"Contestabile","year":"2007","journal-title":"Hippocampus"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.freeradbiomed.2017.07.026","article-title":"Neurogenesis impairment: An early developmental defect in Down syndrome","volume":"114","author":"Stagni","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1242\/dev.066167","article-title":"Transient expression ofMnb\/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling","volume":"138","author":"Hammerle","year":"2011","journal-title":"Development"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nrc3556","article-title":"The DREAM complex: Master coordinator of cell cycle-dependent gene expression","volume":"13","author":"Sadasiva","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1101\/gad.2034211","article-title":"DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly","volume":"25","author":"Litovchick","year":"2011","journal-title":"Genes Dev."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1523\/JNEUROSCI.4711-09.2010","article-title":"Dyrk1A overexpression inhibits proliferation and induces premature neuronal differentiation of neural progenitor cells","volume":"30","author":"Yabut","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.molcel.2013.09.009","article-title":"Dosage of Dyrk1A shifts cells within a p21-cyclin D1 signalling map to control the decision to enter the cell cycle","volume":"52","author":"Chen","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ceb.2009.08.009","article-title":"Dynamic regulation of Notch signaling in neural progenitor cells","volume":"21","author":"Kageyama","year":"2009","journal-title":"Curr. Opin. Cell. Biol."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jns.2006.01.007","article-title":"Notch-1 immunoexpression is increased in Alzheimer\u2019s and Pick\u2019s disease","volume":"244","author":"Nagarsheth","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_314","first-page":"1451","article-title":"Activation of the Notch pathway in Down syndrome: Cross-talk of Notch and APP","volume":"19","author":"Fischer","year":"2005","journal-title":"FASEB J."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0896-6273(00)00028-3","article-title":"Up a notch: Instructing gliogenesis minireview","volume":"27","author":"Wang","year":"2000","journal-title":"Neuron"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1101\/gad.226381.113","article-title":"Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in neocortical progenitor cells","volume":"27","author":"Kurabayashi","year":"2013","journal-title":"Genes Dev."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.lfs.2014.02.014","article-title":"The role of mTOR in depression and antidepressant responses","volume":"101","author":"Abelaira","year":"2014","journal-title":"Life Sci."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.celrep.2014.04.048","article-title":"Selective activation of mTORC1 signaling recapitulates microcephaly, tuberous sclerosis, and neurodegenerative diseases","volume":"7","author":"Kassai","year":"2014","journal-title":"Cell Rep."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrn1078","article-title":"Neurotrophins and their receptors: A convergence point for many signalling pathways","volume":"4","author":"Chao","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nrn1727","article-title":"Functions and mechanisms of retrograde neurotrophin signaling","volume":"6","author":"Zweifel","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/CS20050163","article-title":"Neurotrophin signalling in health and disease","volume":"110","author":"Chao","year":"2006","journal-title":"Clin. Sci."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.brainresrev.2008.07.007","article-title":"New insights into brain BDNF function in normal aging and Alzheimer disease","volume":"59","author":"Aliaga","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1073\/pnas.0510750103","article-title":"Defective cerebellar response to mitogenic Hedgehog signaling in Down syndrome mice","volume":"103","author":"Roper","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1093\/hmg\/ddr033","article-title":"APP-dependent up-regulation of Ptch1 underlies proliferation impairment of neural precursors in Down syndrome","volume":"20","author":"Trazzi","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"20817","DOI":"10.1074\/jbc.M113.451088","article-title":"The amyloid precursor protein (APP) triplicated gene impairs neuronal precursor differentiation and neurite development through two different domains in the Ts65Dn mouse model for Down syndrome","volume":"288","author":"Trazzi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.febslet.2013.05.010","article-title":"The amyloid precursor protein: A biochemical enigma in brain development, function and disease","volume":"587","author":"Nalivaeva","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.nbd.2015.08.001","article-title":"Inhibition of APP gamma-secretase restores sonic hedgehog signaling and neurogenesis in the Ts65Dn mouse model of Down syndrome","volume":"82","author":"Giacomini","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_328","first-page":"3822","article-title":"Overexpression of the DYRK1A Gene (Dual-Specificity Tyrosine Phosphorylation- Regulated Kinase 1A) Induces Alterations of the Serotoninergic and Dopaminergic Processing in Murine Brain Tissues","volume":"55","author":"London","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"25177","DOI":"10.1074\/jbc.M114.567610","article-title":"Synergistic regulation of glutamatergic transmission by serotonin and norepinephrine reuptake inhibitors in prefrontal cortical neurons","volume":"289","author":"Yuen","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.brainres.2016.01.005","article-title":"Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex","volume":"1641","author":"Xing","year":"2016","journal-title":"Brain Res."},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1093\/hmg\/ddm374","article-title":"DSCR1\/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: Implications for Down syndrome and Alzheimer\u2019s disease","volume":"1","author":"Keating","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/jnc.12086","article-title":"RCAN1 regulates vesicle recycling and quantal release kinetics via effects on calcineurin activity","volume":"124","author":"Zanin","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/1440-1681.12884","article-title":"The neural and endocrine roles of RCAN1 in health and disease","volume":"45","author":"Peiris","year":"2018","journal-title":"Clin. Exp. Pharm. Physiol"},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.pharmthera.2018.09.010","article-title":"DYRK1A and cognition: A lifelong relationship","volume":"194","author":"Thomazeau","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1128\/MCB.00394-08","article-title":"Sprouty2-mediated inhibition of fibroblast growth factor signaling is modulated by the protein kinase DYRK1A","volume":"28","author":"Aranda","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1242\/jcs.086124","article-title":"Dyrk1A negatively regulates the actin cytoskeleton through threonine phosphorylation of N-WASP","volume":"125","author":"Park","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/hmg\/ddp047","article-title":"DYRK1A interacts with the REST\/NRSF-SWI\/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome","volume":"18","author":"Zvara","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/cercor\/bhr362","article-title":"Dyrk1A influences neuronal morphogenesis through regulation of cytoskeletal dynamics in mammalian cortical neurons","volume":"22","author":"Calvo","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref_339","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000321994","article-title":"Overexpression of Dyrk1A causes the defects in synaptic vesicle endocytosis","volume":"18","author":"Kim","year":"2010","journal-title":"Neurosignals"},{"key":"ref_340","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/nn.3256","article-title":"Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number","volume":"15","author":"Kwon","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.nbd.2010.06.011","article-title":"Engineering DYRK1A overdosage yields Down syndrome-characteristic cortical splicing aberrations","volume":"40","author":"Toiber","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1523\/JNEUROSCI.3804-15.2016","article-title":"Dynamin 1- and 3-Mediated Endocytosis Is Essential for the Development of a Large Central Synapse In Vivo","volume":"36","author":"Fan","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_343","doi-asserted-by":"crossref","unstructured":"Garcia-Cerro, S., Martinez, P., Vidal, V., Corrales, A., Florez, J., Vidal, R., Rueda, N., Arbon\u00e9s, M.L., and Mart\u00ednez-Cu\u00e9, C. (2014). Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106572"},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1083\/jcb.201510107","article-title":"DSCR1 is required for both axonal growth cone extension and steering","volume":"213","author":"Wang","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_345","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1046\/j.1471-4159.2003.02294.x","article-title":"Aggregate formation and synaptic abnormality induced by DSCR1","volume":"88","author":"Ma","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_346","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1093\/hmg\/dds134","article-title":"Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory","volume":"21","author":"Martin","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_347","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/PL00000855","article-title":"Molecular genetic analysis of the calcineurin signaling pathways","volume":"58","author":"Sugiura","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_348","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/S0960-9822(98)70297-0","article-title":"Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals","volume":"8","author":"Marks","year":"1998","journal-title":"Curr. Biol."},{"key":"ref_349","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1046\/j.1471-4159.2001.00049.x","article-title":"Protein phosphorylation is required for endocytosis in nerve terminals: Potential role for the dephosphins dynamin I and synaptojanin, but not AP180 or amphiphysin","volume":"76","author":"Cousin","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_350","doi-asserted-by":"crossref","first-page":"5640","DOI":"10.1523\/JNEUROSCI.2202-14.2015","article-title":"DSCAM promotes refinement in the mouse retina through cell death and restriction of exploring dendrites","volume":"35","author":"Li","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_351","first-page":"13537","article-title":"NMDA mediated regulation of DSCAM dendritic local translation is lost in a mouse model of Down\u2019s syndrome","volume":"30","author":"Montesinos","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_352","doi-asserted-by":"crossref","first-page":"e99669","DOI":"10.15252\/embj.201899669","article-title":"Nuclear import of the DSCAM-cytoplasmatic domain drives signaling capable of inhibiting synapse formation","volume":"38","author":"Sache","year":"2019","journal-title":"EMBO J."},{"key":"ref_353","first-page":"re10","article-title":"Intersecting pathways in cell biology","volume":"3","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_354","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000015182","article-title":"Genomic structure, sequence, and refined mapping of the human intersectin gene (itsn), which encompasses 250 kb on chromosome 21q22.1\u2192q22.2","volume":"83","author":"Guipponi","year":"1998","journal-title":"Cytogenet. Cell. Genet."},{"key":"ref_355","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/sj.ejhg.5200356","article-title":"Alu-splice cloning of human intersectin (itsn), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome","volume":"7","author":"Pucharcos","year":"1999","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_356","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.neurobiolaging.2006.11.008","article-title":"Translational gene mapping of cognitive decline","volume":"29","author":"Wilmot","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_357","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.neurobiolaging.2004.09.018","article-title":"Endosome function and dysfunction in Alzheimer\u2019s disease and other neurodegenerative diseases","volume":"26","author":"Nixon","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_358","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1091\/mbc.e05-07-0700","article-title":"Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2","volume":"17","author":"Nishimura","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_359","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41593-019-0419-y","article-title":"Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling","volume":"22","author":"Gunner","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_360","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00401-016-1622-5","article-title":"TREM1 facilitates microglial phagocytosis of amyloid beta","volume":"132","author":"Jiang","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_361","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.tins.2019.03.003","article-title":"A unifying hypothesis for Alzheimer\u2019s disease: From plaques to neurodegeneration","volume":"42","author":"Edwards","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_362","doi-asserted-by":"crossref","first-page":"9359","DOI":"10.1074\/jbc.M707108200","article-title":"Amyloid-beta binds to the extracellular cysteine-richdomain of Frizzled and inhibits Wnt\/beta-catenin signaling","volume":"283","author":"Magdesian","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_363","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1007\/s12035-017-0818-6","article-title":"Down syndrome iPSC-derived astrocytes impair neuronal synaptogenesis and the mTOR pathway in vitro","volume":"55","author":"Araujo","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_364","doi-asserted-by":"crossref","first-page":"11441","DOI":"10.1523\/JNEUROSCI.1283-12.2012","article-title":"Multiple roles for mammalian target of rapamycin signaling in both glutamatergic and GABAergic synaptic transmission","volume":"32","author":"Weston","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_365","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.tibs.2013.10.001","article-title":"Signaling interplay between transforming growth factor-beta receptor and PI3K\/AKT pathways in cancer","volume":"38","author":"Zhang","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_366","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1007\/s11064-017-2399-1","article-title":"PI3K\/Akt and ERK\/MAPK Signaling Promote Different Aspects of Neuron Survival and Axonal Regrowth Following Rat Facial Nerve Axotomy","volume":"42","author":"Huang","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_367","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuroscience.2020.04.019","article-title":"G-protein coupled receptors and tau-different roles in Alzheimer\u2019s disease","volume":"438","author":"Chidambaram","year":"2020","journal-title":"Neuroscience"},{"key":"ref_368","doi-asserted-by":"crossref","unstructured":"Duka, V., Lee, J.-H., Credle, J., Wills, J., Oaks, A., Smolinsky, C., Shah, K., Mash, D.C., Masliah, E., and Sidhu, A. (2013). Identification of the sites of tau hyperphosphorylation and activation of tau kinases in synucleinopathies and Alzheimer\u2019s diseases. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075025"},{"key":"ref_369","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1007\/s12035-016-0269-5","article-title":"Targeting CCR3 to reduce amyloid-b production, Tau hyperphosphorylation, and synaptic loss in a mouse model of Alzheimer\u2019s disease","volume":"54","author":"Zhu","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_370","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nrn2977","article-title":"The role of G protein-coupled receptors in the pathology of Alzheimer\u2019s disease","volume":"12","author":"Thathiah","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_371","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic glutamate receptors: Physiology, pharmacology, and disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_372","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nrn2572","article-title":"The molecular and cellular biology of enhanced cognition","volume":"10","author":"Lee","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_373","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/bs.pbr.2019.10.001","article-title":"Translational validity and implications of pharmacotherapies in preclinical models of Down syndrome","volume":"251","author":"Rueda","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_374","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/ana.25410","article-title":"Amyloid-\u03b2 immunotherapy for alzheimer disease: Is it now a long shot?","volume":"85","author":"Panza","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_375","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.nutres.2015.02.007","article-title":"Fish oil improves gene targets of Down syndrome in C57BL and BALB\/c mice","volume":"35","author":"Zmijewski","year":"2015","journal-title":"Nutr. Res."},{"key":"ref_376","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2174\/0929867043455576","article-title":"Inhibitors of the calcineurin\/NFAT pathway","volume":"11","author":"Redondo","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_377","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12035-013-8505-8","article-title":"Targeting the mTOR signaling network for Alzheimer\u2019s disease therapy","volume":"49","author":"Wang","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_378","doi-asserted-by":"crossref","first-page":"118020","DOI":"10.1016\/j.lfs.2020.118020","article-title":"The role of CREB and BDNF in neurobiology and treatment of Alzheimer\u2019s disease","volume":"257","author":"Amidfar","year":"2020","journal-title":"Life Sci."},{"key":"ref_379","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.1007\/s12035-019-1469-6","article-title":"Procyanidins and Alzheimer\u2019s Disease","volume":"56","author":"Zhao","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_380","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41582-018-0013-z","article-title":"Tau-targeting therapies for Alzheimer disease","volume":"14","author":"Congdon","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_381","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.pharmthera.2013.01.004","article-title":"GDNF, NGF and BDNF as therapeutic options for neurodegeneration","volume":"138","author":"Allen","year":"2013","journal-title":"Pharm. Ther."},{"key":"ref_382","first-page":"228","article-title":"Alzheimer\u2019s disease: Early diagnosis and treatment","volume":"18","author":"Chu","year":"2012","journal-title":"Hong Kong Med. J."},{"key":"ref_383","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/BST20170501","article-title":"Mitochondrial abnormalities in Parkinson\u2019s disease and Alzheimer\u2019s disease: Can mitochondria be targeted therapeutically?","volume":"46","author":"Macdonald","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_384","doi-asserted-by":"crossref","first-page":"100936","DOI":"10.1016\/j.arr.2019.100936","article-title":"Diabetes drugs in the fight against Alzheimer\u2019s disease","volume":"54","author":"Boccardi","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_385","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s12035-010-8137-1","article-title":"Why pleiotropic interventions are needed for Alzheimer\u2019s disease","volume":"41","author":"Frautschy","year":"2010","journal-title":"Mol. Neurobiol."},{"key":"ref_386","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/JLB.MR0818-319R","article-title":"Microglia in Alzheimer\u2019s disease: A target for immunotherapy","volume":"106","author":"Wang","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_387","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3233\/JAD-180766","article-title":"Treatment Combinations for Alzheimer\u2019s Disease: Current and Future Pharmacotherapy Options","volume":"67","author":"Cummings","year":"2019","journal-title":"J. Alzheimers Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6906\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:11:52Z","timestamp":1760177512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,20]]},"references-count":387,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21186906"],"URL":"https:\/\/doi.org\/10.3390\/ijms21186906","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,20]]}}}