{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:28:00Z","timestamp":1785911280429,"version":"3.56.0"},"reference-count":158,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["AARG-22-974669"],"award-info":[{"award-number":["AARG-22-974669"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["00128"],"award-info":[{"award-number":["00128"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}]},{"name":"NIH","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}]},{"name":"NIH","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}]},{"name":"NIH","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}]},{"name":"NIH","award":["AARG-22-974669"],"award-info":[{"award-number":["AARG-22-974669"]}]},{"name":"NIH","award":["00128"],"award-info":[{"award-number":["00128"]}]},{"name":"LeJeune Foundation","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}]},{"name":"LeJeune Foundation","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}]},{"name":"LeJeune Foundation","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}]},{"name":"LeJeune Foundation","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}]},{"name":"LeJeune Foundation","award":["AARG-22-974669"],"award-info":[{"award-number":["AARG-22-974669"]}]},{"name":"LeJeune Foundation","award":["00128"],"award-info":[{"award-number":["00128"]}]},{"name":"Alzheimer\u2019s Association","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}]},{"name":"Alzheimer\u2019s Association","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}]},{"name":"Alzheimer\u2019s Association","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}]},{"name":"Alzheimer\u2019s Association","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}]},{"name":"Alzheimer\u2019s Association","award":["AARG-22-974669"],"award-info":[{"award-number":["AARG-22-974669"]}]},{"name":"Alzheimer\u2019s Association","award":["00128"],"award-info":[{"award-number":["00128"]}]},{"name":"Infectious Diseases Society of America","award":["CA2018010"],"award-info":[{"award-number":["CA2018010"]}]},{"name":"Infectious Diseases Society of America","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}]},{"name":"Infectious Diseases Society of America","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}]},{"name":"Infectious Diseases Society of America","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}]},{"name":"Infectious Diseases Society of America","award":["AARG-22-974669"],"award-info":[{"award-number":["AARG-22-974669"]}]},{"name":"Infectious Diseases Society of America","award":["00128"],"award-info":[{"award-number":["00128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer\u2019s disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread. This review is focused on current findings regarding p-Tau and its potential to seed pathology as a \u201cprion-like\u201d spreader. It also considers the consequences of p-Tau pathology leading to AD, particularly in individuals with Down syndrome. Methods: Scopus (SC) and PubMed (PM) were searched in English using keywords \u201ctau AND seeding AND brain AND down syndrome\u201d. A total of 558 SC or 529 PM potentially relevant articles were identified, of which only six SC or three PM articles mentioned Down syndrome. This review was built upon the literature and the recent findings of our group and others. Results: Misfolded p-Tau isoforms are seeding competent and may be responsible for spreading AD pathology. Conclusions: This review demonstrates recent work focused on understanding the role of neurofibrillary tangles and monomeric\/oligomeric Tau in the prion-like spreading of Tau pathology in the human brain.<\/jats:p>","DOI":"10.3390\/jcm13051338","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T03:35:48Z","timestamp":1709004948000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Role of Tau Pathology in Alzheimer\u2019s Disease and Down Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-7599","authenticated-orcid":false,"given":"Ann-Charlotte","family":"Granholm","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-7949","authenticated-orcid":false,"given":"Eric D.","family":"Hamlett","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alldred, M.J., Martini, A.C., Patterson, D., Hendrix, J., and Granholm, A.C. (2021). Aging with Down Syndrome\u2014Where Are We Now and Where Are We Going?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10204687"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000449049","article-title":"Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society","volume":"7","author":"Delabar","year":"2016","journal-title":"Mol. Syndromol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/1567205012666151020114607","article-title":"Aging in Down Syndrome and the Development of Alzheimer\u2019s Disease Neuropathology","volume":"13","author":"Head","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1093\/brain\/awaa326","article-title":"Evolution of neuroinflammation across the lifespan of individuals with Down Syndrome","volume":"143","author":"Iulita","year":"2020","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S1474-4422(21)00245-3","article-title":"Alzheimer\u2019s disease associated with Down Syndrome: A genetic form of dementia","volume":"20","author":"Fortea","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jalz.2014.10.007","article-title":"Down Syndrome and Alzheimer\u2019s disease: Common pathways, common goals","volume":"11","author":"Hartley","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3233\/JAD-2011-111172","article-title":"Overexpression of amyloid-beta protein precursor induces mitochondrial oxidative stress and activates the intrinsic apoptotic cascade","volume":"28","author":"Bartley","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3233\/JAD-180589","article-title":"Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer\u2019s Disease","volume":"67","author":"Helman","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0168-0102(03)00005-1","article-title":"Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down\u2019s syndrome","volume":"45","author":"Hunter","year":"2003","journal-title":"Neurosci. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.biopsych.2011.08.016","article-title":"Neurobiological elements of cognitive dysfunction in Down Syndrome: Exploring the role of APP","volume":"71","author":"Heyn","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.2147\/JIR.S280953","article-title":"Interferon-Driven Immune Dysregulation in Down Syndrome: A Review of the Evidence","volume":"14","author":"Chung","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4766","DOI":"10.1038\/s41467-019-12739-9","article-title":"Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors","volume":"10","author":"Powers","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1365-2249.2011.04335.x","article-title":"Infections and immunodeficiency in Down Syndrome","volume":"164","author":"Ram","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","first-page":"e12113","article-title":"Distribution of microglial phenotypes as a function of age and Alzheimer\u2019s disease neuropathology in the brains of people with Down Syndrome","volume":"12","author":"Martini","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2017.07.009","article-title":"Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism","volume":"114","author":"Barone","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","first-page":"99","article-title":"Opportunities, barriers, and recommendations in Down Syndrome research","volume":"5","author":"Hendrix","year":"2021","journal-title":"Transl. Sci. Rare Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/alz.12112","article-title":"Further understanding the connection between Alzheimer\u2019s disease and Down Syndrome","volume":"16","author":"Snyder","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2212954119","DOI":"10.1073\/pnas.2212954119","article-title":"Abeta and tau prions feature in the neuropathogenesis of Down Syndrome","volume":"119","author":"Condello","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jalz.2016.08.012","article-title":"Neuronal exosomes reveal Alzheimer\u2019s disease biomarkers in Down Syndrome","volume":"13","author":"Hamlett","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/dneu.22712","article-title":"Exosome release and cargo in Down Syndrome","volume":"79","author":"Hamlett","year":"2019","journal-title":"Dev. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ledreux, A., Thomas, S., Hamlett, E.D., Trautman, C., Gilmore, A., Rickman Hager, E., Paredes, D.A., Margittai, M., Fortea, J., and Granholm, A.C. (2021). Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173931"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., and Reddy, P.H. (2022). Phosphorylated Tau in Alzheimer\u2019s Disease and Other Tauopathies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112841"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41586-019-1026-5","article-title":"Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules","volume":"568","author":"Falcon","year":"2019","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1002\/anie.201308473","article-title":"Single mutations in tau modulate the populations of fibril conformers through seed selection","volume":"53","author":"Meyer","year":"2014","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10271","DOI":"10.1021\/ja303498q","article-title":"Conformational basis for asymmetric seeding barrier in filaments of three- and four-repeat tau","volume":"134","author":"Siddiqua","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1152\/physrev.00024.2003","article-title":"Role of tau protein in both physiological and pathological conditions","volume":"84","author":"Avila","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.15252\/embj.201592748","article-title":"Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity","volume":"34","author":"Wegmann","year":"2015","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17336","DOI":"10.1074\/jbc.RA118.005316","article-title":"Structural disorder in four-repeat Tau fibrils reveals a new mechanism for barriers to cross-seeding of Tau isoforms","volume":"293","author":"Weismiller","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","article-title":"Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease","volume":"26","author":"Dujardin","year":"2020","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00702-016-1635-1","article-title":"Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy","volume":"124","author":"Armstrong","year":"2017","journal-title":"J. Neural. Transm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.stem.2022.04.018","article-title":"Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons","volume":"29","author":"Capano","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00401-016-1644-z","article-title":"Widespread tau seeding activity at early Braak stages","volume":"133","author":"Furman","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15317","DOI":"10.1074\/jbc.M110.209296","article-title":"Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles","volume":"286","author":"Guo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00401-021-02317-z","article-title":"A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer\u2019s disease","volume":"142","author":"Gargini","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/0306-4522(94)00598-Y","article-title":"The expression and distribution of tau proteins and messenger RNA in rat dorsal root ganglion neurons during development and regeneration","volume":"66","author":"Nothias","year":"1995","journal-title":"Neuroscience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/BF02736834","article-title":"Microtubule-associated proteins (MAPs) in the peripheral nervous system during development and regeneration","volume":"8","author":"Nunez","year":"1997","journal-title":"J. Mol. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"595532","DOI":"10.3389\/fneur.2020.595532","article-title":"Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation","volume":"11","author":"Alquezar","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3389\/fnagi.2019.00256","article-title":"The Evolution of Tau Phosphorylation and Interactions","volume":"11","author":"Trushina","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34850","DOI":"10.1074\/jbc.M707358200","article-title":"DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down Syndrome and Alzheimer disease","volume":"282","author":"Ryoo","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1038\/s41598-018-20984-z","article-title":"DYRK1A inhibition and cognitive rescue in a Down Syndrome mouse model are induced by new fluoro-DANDY derivatives","volume":"8","author":"Neumann","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00018-020-03626-4","article-title":"DYRK1A: A Down Syndrome-related dual protein kinase with a versatile role in tumorigenesis","volume":"78","author":"Laham","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","unstructured":"Feki, A., and Hibaoui, Y. (2018). DYRK1A Protein, A Promising Therapeutic Target to Improve Cognitive Deficits in Down Syndrome. Brain Sci., 8.","DOI":"10.3390\/brainsci8100187"},{"key":"ref_44","first-page":"839","article-title":"A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition","volume":"9","author":"Kim","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13000","DOI":"10.1111\/acel.13000","article-title":"Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer\u2019s disease","volume":"18","author":"Melchior","year":"2019","journal-title":"Aging Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15847","DOI":"10.1038\/s41598-022-19967-y","article-title":"DYRK1A antagonists rescue degeneration and behavioural deficits of in vivo models based on amyloid-beta, Tau and DYRK1A neurotoxicity","volume":"12","author":"Zhu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.neuron.2021.03.026","article-title":"Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components","volume":"109","author":"Lester","year":"2021","journal-title":"Neuron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13326","DOI":"10.1111\/acel.13326","article-title":"\u201cProtein aggregates\u201d contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation","volume":"20","author":"Atluri","year":"2021","journal-title":"Aging Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, X., Lin, Y., Eschmann, N.A., Zhou, H., Rauch, J.N., Hernandez, I., Guzman, E., Kosik, K.S., and Han, S. (2017). RNA stores tau reversibly in complex coacervates. PLoS Biol., 15.","DOI":"10.1101\/111245"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1021\/acs.biochem.5b00453","article-title":"RNA Binds to Tau Fibrils and Sustains Template-Assisted Growth","volume":"54","author":"Dinkel","year":"2015","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41467-017-00480-0","article-title":"Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau","volume":"8","author":"Ambadipudi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.celrep.2019.08.104","article-title":"Tau-Mediated Disruption of the Spliceosome Triggers Cryptic RNA Splicing and Neurodegeneration in Alzheimer\u2019s Disease","volume":"29","author":"Hsieh","year":"2019","journal-title":"Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1074\/mcp.M115.050724","article-title":"The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome","volume":"14","author":"Gunawardana","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/ana.410410211","article-title":"Sequestration of RNA in Alzheimer\u2019s disease neurofibrillary tangles and senile plaques","volume":"41","author":"Ginsberg","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zwierzchowski-Zarate, A.N., Mendoza-Oliva, A., Kashmer, O.M., Collazo-Lopez, J.E., White, C.L., and Diamond, M.I. (2022). RNA induces unique tau strains and stabilizes Alzheimer\u2019s disease seeds. J. Biol. Chem., 298.","DOI":"10.1101\/2022.01.29.478315"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25578","DOI":"10.18632\/aging.203738","article-title":"G-Quadruplexes and the DNA\/RNA helicase DHX36 in health, disease, and aging","volume":"13","author":"Antcliff","year":"2021","journal-title":"Aging"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1164057","DOI":"10.3389\/fragi.2023.1164057","article-title":"G-quadruplexes and associated proteins in aging and Alzheimer\u2019s disease","volume":"4","author":"Morales","year":"2023","journal-title":"Front. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-021-00449-0","article-title":"Beyond association: Successes and challenges in linking non-coding genetic variation to functional consequences that modulate Alzheimer\u2019s disease risk","volume":"16","author":"Novikova","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/1874609815666220126095847","article-title":"Role of Long Non-coding RNAs in the Pathogenesis of Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"15","author":"Sivagurunathan","year":"2022","journal-title":"Curr. Aging Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Canseco-Rodriguez, A., Masola, V., Aliperti, V., Meseguer-Beltran, M., Donizetti, A., and Sanchez-Perez, A.M. (2022). Long Non-Coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202209.0204.v1"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Olufunmilayo, E.O., and Holsinger, R.M.D. (2023). Roles of Non-Coding RNA in Alzheimer\u2019s Disease Pathophysiology. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512498"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"821002","DOI":"10.3389\/fnmol.2021.821002","article-title":"Long Non-coding RNA: Insight Into Mechanisms of Alzheimer\u2019s Disease","volume":"14","author":"Lan","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"742242","DOI":"10.3389\/fnagi.2021.742242","article-title":"Molecular Insight Into the Therapeutic Potential of Long Non-coding RNA-Associated Competing Endogenous RNA Axes in Alzheimer\u2019s Disease: A Systematic Scoping Review","volume":"13","author":"Sabaie","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4816","DOI":"10.1093\/nar\/gkab164","article-title":"G-Quadruplexes as pathogenic drivers in neurodegenerative disorders","volume":"49","author":"Wang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e49735","DOI":"10.15252\/embr.201949735","article-title":"G-Quadruplexes act as sequence-dependent protein chaperones","volume":"21","author":"Begeman","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kallweit, L., Hamlett, E.D., Saternos, H., Gilmore, A., Granholm, A.C., and Horowitz, S. (2023). A New Role for RNA G-quadruplexes in Aging and Alzheimer\u2019s Disease. bioRxiv.","DOI":"10.1101\/2023.10.02.560545"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bbrc.2020.01.145","article-title":"Identification and immunohistochemical characterization of G-quadruplexes in mouse brain","volume":"531","author":"Asamitsu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3233\/JAD-2008-14407","article-title":"Truncation of tau protein and its pathological significance in Alzheimer\u2019s disease","volume":"14","year":"2008","journal-title":"J. Alzheimers Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13812","DOI":"10.1074\/jbc.RA120.012587","article-title":"Truncation of Tau selectively facilitates its pathological activities","volume":"295","author":"Gu","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hamano, T., Enomoto, S., Shirafuji, N., Ikawa, M., Yamamura, O., Yen, S.H., and Nakamoto, Y. (2021). Autophagy and Tau Protein. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147475"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e36584","DOI":"10.7554\/eLife.36584","article-title":"Inert and seed-competent tau monomers suggest structural origins of aggregation","volume":"7","author":"Mirbaha","year":"2018","journal-title":"Elife"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Mirbaha, H., Chen, D., Mullapudi, V., Terpack, S.J., White, C.L., Joachimiak, L.A., and Diamond, M.I. (2022). Seed-competent tau monomer initiates pathology in a tauopathy mouse model. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102163"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nature01832","article-title":"Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration","volume":"424","author":"Liou","year":"2003","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nrm2261","article-title":"The prolyl isomerase PIN1: A pivotal new twist in phosphorylation signalling and disease","volume":"8","author":"Lu","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature14658","article-title":"Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy","volume":"523","author":"Kondo","year":"2015","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1093\/jnen\/nlx101","article-title":"Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies","volume":"77","author":"Kenney","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-0716-2655-9_16","article-title":"Abeta and Tau Prions Causing Alzheimer\u2019s Disease","volume":"2561","author":"Condello","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1021\/bi2004685","article-title":"Variations in filament conformation dictate seeding barrier beween three- and four-repeat tau","volume":"50","author":"Dinkel","year":"2011","journal-title":"Biochemistry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-4939-6598-4_9","article-title":"Tau Oligomers as Pathogenic Seeds: Preparation and Propagation In Vitro and In Vivo","volume":"1523","author":"Gerson","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-neuro-072116-031153","article-title":"Propagation of Tau Aggregates and Neurodegeneration","volume":"40","author":"Goedert","year":"2017","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e20210542","DOI":"10.1084\/jem.20210542","article-title":"Activated microglia mitigate Abeta-associated tau seeding and spreading","volume":"218","author":"Gratuze","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00401-023-02600-1","article-title":"Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau","volume":"146","author":"Welikovitch","year":"2023","journal-title":"Acta Neuropathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.pnpbp.2014.05.004","article-title":"Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down Syndrome","volume":"54","author":"Das","year":"2014","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.brainres.2017.09.035","article-title":"Assessing disease-modifying effects of norepinephrine in Down Syndrome and Alzheimer\u2019s disease","volume":"1702","author":"Ponnusamy","year":"2019","journal-title":"Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1006\/exnr.1999.7289","article-title":"Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down\u2019s syndrome","volume":"161","author":"Granholm","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_86","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_87","doi-asserted-by":"crossref","first-page":"703876","DOI":"10.3389\/fnagi.2021.703876","article-title":"Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer\u2019s Disease","volume":"13","author":"Martinez","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1046\/j.1471-4159.2000.741185.x","article-title":"Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down\u2019s syndrome","volume":"74","author":"Sendera","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/ana.410070512","article-title":"Neurofibrillary tangles, granulovacuolar degeneration, and neuron loss in Down Syndrome: Quantitative comparison with Alzheimer dementia","volume":"7","author":"Ball","year":"1980","journal-title":"Ann. Neurol."},{"key":"ref_90","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_91","first-page":"1501","article-title":"GABAA receptor subunit deregulation in the hippocampus of human foetuses with Down Syndrome","volume":"223","author":"Milenkovic","year":"2018","journal-title":"Brain Struct. Funct."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00401-001-0471-y","article-title":"Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down Syndrome","volume":"103","author":"Wegiel","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.brainres.2010.09.107","article-title":"Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice","volume":"1366","author":"Yu","year":"2010","journal-title":"Brain Res."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_96","first-page":"2","article-title":"Revisiting the Cholinergic Hypothesis in Alzheimer\u2019s Disease: Emerging Evidence from Translational and Clinical Research","volume":"6","author":"Hampel","year":"2019","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00401-019-01965-6","article-title":"Frontal cortex and striatal cellular and molecular pathobiology in individuals with Down Syndrome with and without dementia","volume":"137","author":"Perez","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"l6217","DOI":"10.1136\/bmj.l6217","article-title":"Cognitive symptoms of Alzheimer\u2019s disease: Clinical management and prevention","volume":"367","author":"Joe","year":"2019","journal-title":"BMJ"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1755-5949.2010.00175.x","article-title":"Beyond the cholinergic hypothesis: Do current drugs work in Alzheimer\u2019s disease?","volume":"16","author":"Martorana","year":"2010","journal-title":"CNS Neurosci. Ther."},{"key":"ref_100","first-page":"1479","article-title":"Cholinesterase inhibitors as Alzheimer\u2019s therapeutics (Review)","volume":"20","author":"Sharma","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1192\/bjp.2017.21","article-title":"Impact of cholinesterase inhibitors or memantine on survival in adults with Down Syndrome and dementia: Clinical cohort study","volume":"212","author":"Eady","year":"2018","journal-title":"Br. J. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1016\/j.ajpath.2011.07.044","article-title":"Progression of tau pathology in cholinergic Basal forebrain neurons in mild cognitive impairment and Alzheimer\u2019s disease","volume":"179","author":"Vana","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2174\/1567205012666150921095924","article-title":"Noradrenergic System in Down Syndrome and Alzheimer\u2019s Disease A Target for Therapy","volume":"13","author":"Phillips","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1523\/JNEUROSCI.1483-17.2017","article-title":"Locus Coeruleus Ablation Exacerbates Cognitive Deficits, Neuropathology, and Lethality in P301S Tau Transgenic Mice","volume":"38","author":"Chalermpalanupap","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7829507","DOI":"10.1155\/2017\/7829507","article-title":"Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus","volume":"2017","author":"Chalermpalanupap","year":"2017","journal-title":"Neural Plast."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tins.2018.01.010","article-title":"Long Road to Ruin: Noradrenergic Dysfunction in Neurodegenerative Disease","volume":"41","author":"Weinshenker","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2174\/157015908785777229","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part I: Principles of functional organisation","volume":"6","author":"Samuels","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"E4376","DOI":"10.1073\/pnas.1411649111","article-title":"Proteopathic tau seeding predicts tauopathy in vivo","volume":"111","author":"Holmes","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.nbd.2017.06.005","article-title":"Novel human neuronal tau model exhibiting neurofibrillary tangles and transcellular propagation","volume":"106","author":"Reilly","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jalz.2014.06.008","article-title":"Identification of preclinical Alzheimer\u2019s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study","volume":"11","author":"Fiandaca","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1096\/fj.201600756R","article-title":"Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer\u2019s disease","volume":"30","author":"Goetzl","year":"2016","journal-title":"FASEB J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/ana.25172","article-title":"High complement levels in astrocyte-derived exosomes of Alzheimer disease","volume":"83","author":"Goetzl","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5804","DOI":"10.1021\/bi501050g","article-title":"Amplification of Tau fibrils from minute quantities of seeds","volume":"53","author":"Meyer","year":"2014","journal-title":"Biochemistry"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Guix, F.X., Corbett, G.T., Cha, D.J., Mustapic, M., Liu, W., Mengel, D., Chen, Z., Aikawa, E., Young-Pearse, T., and Kapogiannis, D. (2018). Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030663"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12445","DOI":"10.1074\/jbc.M115.709485","article-title":"Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner","volume":"291","author":"Polanco","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"18967","DOI":"10.1074\/jbc.H119.011687","article-title":"Leaky endosomes push tau over the seed limit","volume":"294","author":"Ugbode","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"104988","DOI":"10.1016\/j.neuint.2021.104988","article-title":"Role of the endolysosomal pathway and exosome release in tau propagation","volume":"145","author":"Yan","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40478-017-0466-0","article-title":"Enhanced exosome secretion in Down Syndrome brain\u2014A protective mechanism to alleviate neuronal endosomal abnormalities","volume":"5","author":"Gauthier","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3233\/JAD-200900","article-title":"Blood-Based ATN Biomarkers of Alzheimer\u2019s Disease: A Meta-Analysis","volume":"79","author":"Koychev","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_120","first-page":"63","article-title":"Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile","volume":"3","author":"Winston","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3233\/JAD-180776","article-title":"Neuronal Exosome-Derived Human Tau is Toxic to Recipient Mouse Neurons in vivo","volume":"67","author":"Winston","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fnagi.2019.00112","article-title":"Involvement of Oligodendrocytes in Tau Seeding and Spreading in Tauopathies","volume":"11","author":"Ferrer","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Darricau, M., Dou, C., Kinet, R., Zhu, T., Zhou, L., Li, X., Bedel, A., Claverol, S., Tokarski, C., and Katsinelos, T. (2024). Tau seeds from Alzheimer\u2019s disease brains trigger tau spread in macaques while oligomeric-A\u03b2 mediates pathology maturation. Alzheimers Dement., 1\u201319.","DOI":"10.1002\/alz.13604"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.neuron.2019.10.010","article-title":"Amyloid-Beta (Abeta) Plaques Promote Seeding and Spreading of Alpha-Synuclein and Tau in a Mouse Model of Lewy Body Disorders with Abeta Pathology","volume":"105","author":"Bassil","year":"2020","journal-title":"Neuron"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/bpa.12778","article-title":"Relevance of host tau in tau seeding and spreading in tauopathies","volume":"30","author":"Ferrer","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1567205012999151021102914","article-title":"The Link between Alzheimer\u2019s Disease and Down Syndrome. A Historical Perspective","volume":"13","author":"Salehi","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e1919771","DOI":"10.1001\/jamanetworkopen.2019.19771","article-title":"Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium","volume":"3","author":"McCrea","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3233\/JAD-201167","article-title":"Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer\u2019s Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome","volume":"79","author":"Petersen","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S1474-4422(21)00129-0","article-title":"Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down Syndrome: A cohort study","volume":"20","author":"Alcolea","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1001\/jamaneurol.2022.1740","article-title":"Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers","volume":"79","author":"Janelidze","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1212\/WNL.0000000000003246","article-title":"Plasma tau in Alzheimer disease","volume":"87","author":"Mattsson","year":"2016","journal-title":"Neurology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.freeradbiomed.2017.08.028","article-title":"Exosomal biomarkers in Down Syndrome and Alzheimer\u2019s disease","volume":"114","author":"Hamlett","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/370471a0","article-title":"Cell-free formation of protease-resistant prion protein","volume":"370","author":"Kocisko","year":"1994","journal-title":"Nature"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00401-018-1947-3","article-title":"Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease","volume":"137","author":"Kraus","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1073774","DOI":"10.3389\/fnagi.2023.1073774","article-title":"Two simple assays for assessing the seeding activity of proteopathic tau","volume":"15","author":"Liu","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s40478-022-01436-2","article-title":"Tau seeding activity in various regions of Down Syndrome brain assessed by two novel assays","volume":"10","author":"Jin","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s41380-018-0342-8","article-title":"Tau PET imaging in neurodegenerative tauopathies-still a challenge","volume":"24","author":"Leuzy","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3233\/JAD-170390","article-title":"PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)","volume":"60","author":"Rafii","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_139","first-page":"1","article-title":"Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down Syndrome population","volume":"9","author":"Lao","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"117728","DOI":"10.1016\/j.neuroimage.2021.117728","article-title":"PET measurement of longitudinal amyloid load identifies the earliest stages of amyloid-beta accumulation during Alzheimer\u2019s disease progression in Down Syndrome","volume":"228","author":"Zammit","year":"2021","journal-title":"Neuroimage"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/alz.13444","article-title":"Characterizing the emergence of amyloid and tau burden in Down Syndrome","volume":"20","author":"Zammit","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer\u2019s disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1995","journal-title":"Neurobiol. Aging"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/nan.12406","article-title":"The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down Syndrome","volume":"44","author":"Milenkovic","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13024-020-00414-3","article-title":"Regional binding of tau and amyloid PET tracers in Down Syndrome autopsy brain tissue","volume":"15","author":"Lemoine","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00259-019-04305-8","article-title":"Cross-interaction of tau PET tracers with monoamine oxidase B: Evidence from in silico modelling and in vivo imaging","volume":"46","author":"Murugan","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-022-00533-z","article-title":"Tauopathies: New perspectives and challenges","volume":"17","author":"Zhang","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/s41467-017-01068-4","article-title":"Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae","volume":"8","author":"Albayram","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"100341","DOI":"10.1016\/j.ijchp.2022.100341","article-title":"Abnormal degree centrality and functional connectivity in Down Syndrome: A resting-state fMRI study","volume":"23","author":"Cui","year":"2023","journal-title":"Int. J. Clin. Health Psychol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1225228","DOI":"10.3389\/fnins.2023.1225228","article-title":"Distinct neuroanatomical and neuropsychological features of Down Syndrome compared to related neurodevelopmental disorders: A systematic review","volume":"17","author":"Hamadelseed","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s40478-022-01385-w","article-title":"Neurogenesis and neuronal differentiation in the postnatal frontal cortex in Down Syndrome","volume":"10","author":"Utagawa","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1523\/JNEUROSCI.2281-17.2017","article-title":"The Microtubule-Associated Protein Tau Mediates the Organization of Microtubules and Their Dynamic Exploration of Actin-Rich Lamellipodia and Filopodia of Cortical Growth Cones","volume":"38","author":"Biswas","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1242\/dev.108712","article-title":"Amyloid precursor protein and neural development","volume":"141","author":"Nicolas","year":"2014","journal-title":"Development"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/jnc.12239","article-title":"From synaptic spines to nuclear signaling: Nuclear and synaptic actions of the amyloid precursor protein","volume":"126","author":"Octave","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1007\/s12035-023-03387-8","article-title":"The Role of Tau Proteoforms in Health and Disease","volume":"60","author":"Waheed","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40035-022-00292-3","article-title":"Immunotherapy for Alzheimer\u2019s disease: Targeting beta-amyloid and beyond","volume":"11","author":"Song","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"173554","DOI":"10.1016\/j.ejphar.2020.173554","article-title":"Alzheimer\u2019s disease: Recent treatment strategies","volume":"887","author":"Vaz","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_157","first-page":"48","article-title":"Integrating Biomarker Outcomes into Clinical Trials for Alzheimer\u2019s Disease in Down Syndrome","volume":"8","author":"Rafii","year":"2021","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Aldecoa, I., Barroeta, I., Carroll, S.L., Fortea, J., Gilmore, A., Ginsberg, S.D., Guzman, S.J., Hamlett, E.D., Head, E., and Perez, S.E. (2024). Down Syndrome Biobank Consortium: A perspective. Alzheimers Dement., 1\u201311.","DOI":"10.1002\/alz.13692"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/5\/1338\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:05:24Z","timestamp":1760105124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/5\/1338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":158,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["jcm13051338"],"URL":"https:\/\/doi.org\/10.3390\/jcm13051338","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]}}}