{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:00:41Z","timestamp":1784257241621,"version":"3.55.0"},"reference-count":114,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>MicroRNAs (miRNAs) are small non-coding nucleic acids that can regulate post-transcriptional gene expression by binding to complementary sequences of target mRNA. Evidence showed that dysregulated miRNA expression may be associated with neurological conditions such as Alzheimer\u2019s disease (AD). In this study, we combined the results of two independent systematic reviews aiming to unveil the co-expression network of miRNAs and proteins in brain tissues of AD patients. Twenty-eight studies including a total of 113 differentially expressed miRNAs (53 of them validated by qRT-PCR), and 26 studies including a total of 196 proteins differentially expressed in AD brains compared to healthy age matched controls were selected. Pathways analyses were performed on the results of the two reviews and 39 common pathways were identified. A further bioinformatic analysis was performed to match miRNA and protein targets with an inverse relation. This revealed 249 inverse relationships in 28 common pathways, representing new potential targets for therapeutic intervention. A meta-analysis, whenever possible, revealed miR-132-3p and miR-16 as consistently downregulated in late-stage AD across the literature. While no inverse relationships between miR-132-3p and proteins were found, miR-16\u2032s inverse relationship with CLOCK proteins in the circadian rhythm pathway is discussed and therapeutic targets are proposed. The most significant miRNA dysregulated pathway highlighted in this review was the hippo signaling pathway with p = 1.66 \u00d7 10\u22129. Our study has revealed new mechanisms for AD pathogenesis and this is discussed along with opportunities to develop novel miRNA-based drugs to target these pathways.<\/jats:p>","DOI":"10.3390\/cells10123479","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:52:32Z","timestamp":1639086752000},"page":"3479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Co-Expression Network Analysis of Micro-RNAs and Proteins in the Alzheimer\u2019s Brain: A Systematic Review of Studies in the Last 10 Years"],"prefix":"10.3390","volume":"10","author":[{"given":"Rachel","family":"Tasker","sequence":"first","affiliation":[{"name":"Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rowlands","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-6442","authenticated-orcid":false,"given":"Zubair","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Surgical Reconstruction and Microbiology Research Centre, National Institute for Health Research, Queen Elizabeth Hospital, Birmingham B15 2TH, UK"},{"name":"Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-4723","authenticated-orcid":false,"given":"Valentina","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Surgical Reconstruction and Microbiology Research Centre, National Institute for Health Research, Queen Elizabeth Hospital, Birmingham B15 2TH, UK"},{"name":"Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2020). Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 16, 391\u2013460.","DOI":"10.1002\/alz.12068"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics\u20142020 update: A report from the american heart association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1111\/jgs.16667","article-title":"The effects of dementia care co-management on acute care, hospice, and long-term care utilization","volume":"68","author":"Jennings","year":"2020","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yu, H., Wang, X., He, R., Liang, R., and Zhou, L. (2015). Measuring the caregiver burden of caring for community-residing people with Alzheimer\u2019s disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132168"},{"key":"ref_6","unstructured":"GBD 2016 Dementia Collaborators (2019). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the global burden of disease study 2016. Lancet Neurol., 18, 88\u2013106."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S527","DOI":"10.3233\/JAD-2010-100501","article-title":"Why women have more Alzheimer\u2019s disease than men: Gender and mitochondrial toxicity of amyloid-beta peptide","volume":"20","author":"Lloret","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1001\/archneur.60.2.185","article-title":"Incidence of Alzheimer disease in a biracial urban community: Relation to apolipoprotein E allele status","volume":"60","author":"Evans","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jalz.2018.06.3063","article-title":"Racial and ethnic estimates of Alzheimer\u2019s disease and related dementias in the United States (2015\u20132060) in adults aged \u226565 years","volume":"15","author":"Matthews","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1136\/bmj.308.6944.1604","article-title":"Cardiovascular disease and distribution of cognitive function in elderly people: The rotterdam study","volume":"308","author":"Breteler","year":"1994","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1001\/archpsyc.64.2.234","article-title":"Loneliness and risk of Alzheimer disease","volume":"64","author":"Wilson","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1001\/jamaneurol.2017.1658","article-title":"Associations between midlife vascular risk factors and 25-year incident dementia in the atherosclerosis risk in communities (ARIC) cohort","volume":"74","author":"Gottesman","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"m2031","DOI":"10.1136\/bmj.m2031","article-title":"Recommended physical activity and all cause and cause specific mortality in US adults: Prospective cohort study","volume":"370","author":"Zhao","year":"2020","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0304-3940(85)90439-2","article-title":"Correlation between senile plaque and neurofibrillary tangle counts in cerebral cortex and neuronal counts in cortex and subcortical structures in Alzheimer\u2019s disease","volume":"56","author":"Mann","year":"1985","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-V","article-title":"Amyloid deposition as the central event in the aetiology of Alzheimer\u2019s disease","volume":"12","author":"Hardy","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/jama.2021.11558","article-title":"Recently approved alzheimer drug raises questions that might never be answered","volume":"326","author":"Rubin","year":"2021","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1038\/d41586-018-05719-4","article-title":"The amyloid hypothesis on trial","volume":"559","author":"Makin","year":"2018","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Das","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.canlet.2021.03.025","article-title":"Regulation of nuclear Factor-KappaB (NF-\u03baB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis?","volume":"509","author":"Mirzaei","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109871","DOI":"10.1016\/j.cellsig.2020.109871","article-title":"Lung cancer cells and their sensitivity\/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators","volume":"78","author":"Ashrafizadeh","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119005","DOI":"10.1016\/j.lfs.2020.119005","article-title":"The role of microRNA-338-3p in cancer: Growth, invasion, chemoresistance, and mediators","volume":"268","author":"Mirzaei","year":"2021","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Catalanotto, C., Cogoni, C., and Zardo, G. (2016). MicroRNA in control of gene expression: An overview of nuclear functions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101712"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cao, D.D., Li, L., and Chan, W.Y. (2016). MicroRNAs: Key regulators in the central nervous system and their implication in neurological diseases. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060842"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.tins.2012.01.004","article-title":"MicroRNAs in neuronal function and dysfunction","volume":"35","author":"Im","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_26","first-page":"406561","article-title":"MicroRNAs and the regulation of tau metabolism","volume":"2012","author":"Sergeant","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.brainres.2016.05.026","article-title":"Expression of microRNA-34a in Alzheimer\u2019s disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity","volume":"1646","author":"Sarkar","year":"2016","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41380-018-0266-3","article-title":"Novel upregulation of amyloid-\u03b2 precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5\u2032-untranslated region: Implications in Alzheimer\u2019s disease","volume":"24","author":"Long","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01627","DOI":"10.1002\/brb3.1627","article-title":"Mechanism of microRNA-22 in regulating neuroinflammation in Alzheimer\u2019s disease","volume":"10","author":"Han","year":"2020","journal-title":"Brain Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/JAD-2010-091603","article-title":"MiR-107 is reduced in Alzheimer\u2019s disease brain neocortex: Validation study","volume":"21","author":"Nelson","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.toxlet.2011.11.032","article-title":"The miR-124 regulates the expression of BACE1\/\u03b2-secretase correlated with cell death in Alzheimer\u2019s disease","volume":"209","author":"Fang","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00401-018-1880-5","article-title":"MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways","volume":"136","author":"Li","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1097\/WNR.0000000000001118","article-title":"MiR-16 attenuates \u03b2-amyloid-induced neurotoxicity through targeting \u03b2-site amyloid precursor protein-cleaving enzyme 1 in an Alzheimer\u2019s disease cell model","volume":"29","author":"Zhong","year":"2018","journal-title":"Neuroreport"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3389\/fgene.2019.00478","article-title":"The Potential for microRNA Therapeutics and Clinical Research","volume":"10","author":"Hanna","year":"2019","journal-title":"Front Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.2174\/1389557520666200513122357","article-title":"Systematic review of current progresses in the nucleic acid-based therapies for neurodegeneration with implications for Alzheimer\u2019s disease","volume":"20","author":"Ghaffari","year":"2020","journal-title":"Mini. Rev. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.5640\/insc.0104169","article-title":"Nanotechnology for Alzheimer\u2019s disease detection and treatment","volume":"1","author":"Nazem","year":"2011","journal-title":"Insci. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1126\/science.1178178","article-title":"Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection","volume":"327","author":"Lanford","year":"2010","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e011458","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS)","volume":"6","author":"Downes","year":"2016","journal-title":"BMJ Open"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The cochrane collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"W498","DOI":"10.1093\/nar\/gks494","article-title":"DIANA miRPath v.2.0: Investigating the combinatorial effect of microRNAs in pathways","volume":"40","author":"Vlachos","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W169","DOI":"10.1093\/nar\/gkt393","article-title":"DIANA-microT web server v5.0: Service integration into miRNA functional analysis workflows","volume":"41","author":"Paraskevopoulou","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1038\/s41598-018-22701-2","article-title":"Whole transcriptome profiling of late-onset Alzheimer\u2019s disease patients provides insights into the molecular changes involved in the disease","volume":"8","author":"Annese","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1766822","DOI":"10.1080\/20013078.2020.1766822","article-title":"Small RNA fingerprinting of Alzheimer\u2019s disease frontal cortex extracellular vesicles and their comparison with peripheral extracellular vesicles","volume":"9","author":"Cheng","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chopra, N., Wang, R., Maloney, B., Nho, K., Beck, J.S., Pourshafie, N., Niculescu, A., Saykin, A.J., Rinaldi, C., and Counts, S.E. (2020). MicroRNA-298 reduces levels of human amyloid-\u03b2 precursor protein (APP), \u03b2-site APP-converting enzyme 1 (BACE1) and specific tau protein moieties. Mol. Psychiatry.","DOI":"10.1038\/s41380-019-0610-2"},{"key":"ref_46","first-page":"156","article-title":"Tumour necrosis factor-\u03b1 (TNF-\u03b1) and miRNA expression in frontal and temporal neocortex in Alzheimer\u2019s disease and the effect of TNF-\u03b1 on miRNA expression in vitro","volume":"2","author":"Culpan","year":"2011","journal-title":"Int. J. Mol. Epidemiol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"91551","DOI":"10.18632\/oncotarget.21177","article-title":"miR-15b represses BACE1 expression in sporadic Alzheimer\u2019s disease","volume":"8","author":"Gong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3233\/JAD-122350","article-title":"A study of small RNAs from cerebral neocortex of pathology-verified Alzheimer\u2019s disease, dementia with lewy bodies, hippocampal sclerosis, frontotemporal lobar dementia, and non-demented human controls","volume":"35","author":"Wang","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111352","DOI":"10.1016\/j.mad.2020.111352","article-title":"Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer\u2019s disease","volume":"191","author":"Henriques","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fnagi.2018.00041","article-title":"MicroRNA-455-3p as a Potential Biomarker for Alzheimer\u2019s disease: An update","volume":"10","author":"Kumar","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1093\/hmg\/ddx267","article-title":"MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer\u2019s disease","volume":"26","author":"Kumar","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1002\/emmm.201201974","article-title":"Alteration of the microRNA network during the progression of Alzheimer\u2019s disease","volume":"5","author":"Lau","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_53","first-page":"1565","article-title":"Downregulated miR-29c correlates with increased BACE1 expression in sporadic Alzheimer\u2019s disease","volume":"8","author":"Lei","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9936","DOI":"10.1002\/jcb.28276","article-title":"miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3\u03b2 in Alzheimer\u2019s disease","volume":"120","author":"Li","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_55","first-page":"8523","article-title":"MicroRNA-132 promotes neurons cell apoptosis and activates Tau phosphorylation by targeting GTDC-1 in Alzheimer\u2019s disease","volume":"23","author":"Liu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s12031-017-0971-4","article-title":"MicroRNA expression in the locus coeruleus, entorhinal cortex, and hippocampus at early and middle stages of braak neurofibrillary tangle pathology","volume":"63","author":"Llorens","year":"2017","journal-title":"J. Mol. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1007\/s12035-016-0002-4","article-title":"The miR-15\/107 Family of microRNA genes regulates CDK5R1\/p35 with Implications for Alzheimer\u2019s disease pathogenesis","volume":"54","author":"Moncini","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.neurobiolaging.2013.07.005","article-title":"MicroRNAs in Alzheimer\u2019s disease: Differential expression in hippocampus and cell-free cerebrospinal fluid","volume":"35","author":"Kuiperij","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2016.09.019","article-title":"The miRNome of Alzheimer\u2019s disease: Consistent downregulation of the miR-132\/212 cluster","volume":"50","author":"Pichler","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1096\/fj.201801846R","article-title":"Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer\u2019s disease","volume":"33","author":"Qian","year":"2019","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1172\/JCI78421","article-title":"Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau","volume":"125","author":"Alaniz","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.biopsych.2017.07.023","article-title":"A novel MicroRNA-124\/PTPN1 signal pathway mediates synaptic and memory deficits in Alzheimer\u2019s disease","volume":"83","author":"Wang","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1093\/hmg\/ddt164","article-title":"De-repression of FOXO3a death axis by microRNA-132 and -212 causes neuronal apoptosis in Alzheimer\u2019s disease","volume":"22","author":"Wong","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00702-019-02134-5","article-title":"MicroRNA-425-5p promotes tau phosphorylation and cell apoptosis in Alzheimer\u2019s disease by targeting heat shock protein B8","volume":"127","author":"Yuan","year":"2020","journal-title":"J. Neural. Transm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"272","DOI":"10.18632\/aging.100887","article-title":"Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer\u2019s disease","volume":"8","author":"Zhang","year":"2016","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Alexandrov, P.N., Jaber, V., and Lukiw, W.J. (2016). Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer\u2019s Disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes, 7.","DOI":"10.3390\/genes7120116"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/WNR.0b013e32835fb6b0","article-title":"Regulation of TREM2 expression by an NF-\u03baB-sensitive miRNA-34a","volume":"24","author":"Zhao","year":"2013","journal-title":"Neuroreport"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1159\/000438925","article-title":"Impaired eukaryotic elongation factor 1A expression in Alzheimer\u2019s disease","volume":"16","author":"Beckelman","year":"2016","journal-title":"Neurodegener. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/j.neurobiolaging.2015.05.020","article-title":"P-glycoprotein expression and amyloid accumulation in human aging and Alzheimer\u2019s disease: Preliminary observations","volume":"36","author":"Chiu","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e01672","DOI":"10.1002\/brb3.1672","article-title":"Alzheimer\u2019s amyloid-\u03b2 and tau protein accumulation is associated with decreased expression of the LDL receptor-associated protein in human brain tissue","volume":"10","author":"Shepherd","year":"2020","journal-title":"Brain Behav."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1017\/S1461145711000149","article-title":"Increased NF-\u03baB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer\u2019s disease","volume":"15","author":"Chen","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.3233\/JAD-132450","article-title":"Bridging integrator 1 (BIN1) protein expression increases in the Alzheimer\u2019s disease brain and correlates with neurofibrillary tangle pathology","volume":"42","author":"Holler","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuroscience.2014.09.052","article-title":"Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer\u2019s disease brains and human microglia","volume":"302","author":"Walker","year":"2015","journal-title":"Neuroscience"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Glennon, E.B., Whitehouse, I.J., Miners, J.S., Kehoe, P.G., Love, S., Kellett, K.A., and Hooper, N.M. (2013). BIN1 is decreased in sporadic but not familial Alzheimer\u2019s disease or in aging. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078806"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/bpa.12597","article-title":"Brain alpha-amylase: A novel energy regulator important in Alzheimer disease?","volume":"28","author":"Byman","year":"2018","journal-title":"Brain Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"ENEURO.0125-20.2020","DOI":"10.1523\/ENEURO.0125-20.2020","article-title":"Altered Expression of the m6A Methyltransferase METTL3 in Alzheimer\u2019s disease","volume":"7","author":"Huang","year":"2020","journal-title":"eNeuro"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Yoo, I.D., Park, M.W., Cha, H.W., Yoon, S., Boonpraman, N., Yi, S.S., and Moon, J.S. (2020). Elevated CLOCK and BMAL1 contribute to the impairment of aerobic glycolysis from astrocytes in Alzheimer\u2019s disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217862"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1750-1326-7-41","article-title":"Mass spectrometry quantification of clusterin in the human brain","volume":"7","author":"Chen","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/bpa.12775","article-title":"Elevation of casein kinase 1\u03b5 associated with TDP-43 and tau pathologies in Alzheimer\u2019s disease","volume":"30","author":"Gu","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s42003-018-0254-9","article-title":"Regional protein expression in human Alzheimer\u2019s brain correlates with disease severity","volume":"2","author":"Xu","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1021\/acschemneuro.7b00410","article-title":"Advanced glycation end products modulate amyloidogenic APP processing and tau phosphorylation: A mechanistic link between glycation and the development of Alzheimer\u2019s disease","volume":"9","author":"Batkulwar","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1111\/jcmm.13998","article-title":"Hippocampal expression of cell-adhesion glycoprotein neuroplastin is altered in Alzheimer\u2019s disease","volume":"23","author":"Ilic","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/bpa.12190","article-title":"TREM2 protein expression changes correlate with Alzheimer\u2019s disease neurodegenerative pathologies in post-mortem temporal cortices","volume":"25","author":"Lue","year":"2015","journal-title":"Brain Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ajmg.b.30993","article-title":"APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure","volume":"153B","author":"Bekris","year":"2010","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.neulet.2010.08.088","article-title":"\u03b2-Amyloid precursor protein and tau protein levels are differently regulated in human cerebellum compared to brain regions vulnerable to Alzheimer\u2019s type neurodegeneration","volume":"485","author":"Farooq","year":"2010","journal-title":"NeuroSci. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3233\/JAD-160220","article-title":"Increased expression of readthrough acetylcholinesterase variants in the brains of Alzheimer\u2019s disease patients","volume":"53","author":"Campanari","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/mp.2016.111","article-title":"Reduced pCREB in Alzheimer\u2019s disease prefrontal cortex is reflected in peripheral blood mononuclear cells","volume":"21","author":"Bartolotti","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1093\/nar\/gks1227","article-title":"CREB regulates the expression of neuronal glucose transporter 3: A possible mechanism related to impaired brain glucose uptake in Alzheimer\u2019s disease","volume":"41","author":"Jin","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12035-019-01754-y","article-title":"Downregulation of 14-3-3 Proteins in Alzheimer\u2019s disease","volume":"57","author":"Gu","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3233\/JAD-2010-101080","article-title":"Regional selectivity of rab5 and rab7 protein upregulation in mild cognitive impairment and Alzheimer\u2019s disease","volume":"22","author":"Ginsberg","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1471-4159.2010.06899.x","article-title":"Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer\u2019s brain","volume":"115","author":"Wang","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s40478-018-0615-0","article-title":"Formation of toxic oligomeric assemblies of RNA-binding protein: Musashi in Alzheimer\u2019s disease","volume":"6","author":"Sengupta","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.2174\/1567205013666160703174254","article-title":"Elevations in the levels of NF-\u03baB and inflammatory chemotactic factors in the brains with Alzheimer\u2019s disease\u2014One mechanism may involve \u03b13 nicotinic acetylcholine receptor","volume":"13","author":"Liao","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrn3208","article-title":"The circadian clock and pathology of the ageing brain","volume":"13","author":"Kondratova","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.288.5466.682","article-title":"Resetting central and peripheral circadian oscillators in transgenic rats","volume":"288","author":"Yamazaki","year":"2000","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-642-25950-0_1","article-title":"Molecular components of the Mammalian circadian clock","volume":"Volume 217","author":"Buhr","year":"2013","journal-title":"Circadian Clocks"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jalz.2016.10.003","article-title":"Circadian alterations during early stages of Alzheimer\u2019s disease are associated with aberrant cycles of DNA methylation in BMAL1","volume":"13","author":"Cronin","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13024-015-0007-x","article-title":"A\u03b2-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer\u2019s disease","volume":"10","author":"Song","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/07420520600827087","article-title":"The circadian regulation of Presenilin-2 gene expression","volume":"23","author":"Belanger","year":"2006","journal-title":"Chronobiol. Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"E6072","DOI":"10.1073\/pnas.1612917113","article-title":"Mammalian period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner","volume":"113","author":"Chiou","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cellsig.2016.12.010","article-title":"Molecular basis for the regulation of the circadian clock kinases CK1\u03b4 and CK1\u03b5","volume":"31","author":"Yang","year":"2017","journal-title":"Cell Signal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"785","DOI":"10.5665\/sleep.3590","article-title":"The circadian clock gene Csnk1e regulates rapid eye movement sleep amount, and nonrapid eye movement sleep architecture in mice","volume":"37","author":"Zhou","year":"2014","journal-title":"Sleep"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/jpet.109.151415","article-title":"Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period","volume":"330","author":"Walton","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0092-8674(03)00557-9","article-title":"The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis","volume":"114","author":"Harvey","year":"2003","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.274027.115","article-title":"Mechanisms of Hippo pathway regulation","volume":"30","author":"Meng","year":"2016","journal-title":"Genes Dev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1101\/gad.1664408","article-title":"TEAD mediates YAP-dependent gene induction and growth control","volume":"22","author":"Zhao","year":"2008","journal-title":"Genes Dev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1042\/BJ20040025","article-title":"Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras","volume":"381","author":"Praskova","year":"2004","journal-title":"Biochem. J."},{"key":"ref_108","first-page":"1455","article-title":"Ubiquitination-deubiquitination in the Hippo signaling pathway","volume":"41","author":"Liu","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1101\/gad.1843810","article-title":"A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)","volume":"24","author":"Zhao","year":"2010","journal-title":"Genes Dev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/1476-4598-13-231","article-title":"Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis","volume":"13","author":"Schittek","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1177\/147323001204000236","article-title":"Comparison of hippocampal volume measured using magnetic resonance imaging in Alzheimer\u2019s disease, vascular dementia, mild cognitive impairment and pseudodementia","volume":"40","author":"Dolek","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fcell.2019.00049","article-title":"Role of hippo pathway-YAP\/TAZ signaling in angiogenesis","volume":"7","author":"Boopathy","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1089\/dna.2019.5308","article-title":"Hippo\/YAP pathway plays a critical role in effect of GDNF against A\u03b2-induced inflammation in microglial cells","volume":"39","author":"Qing","year":"2020","journal-title":"DNA Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4103\/1673-5374.295273","article-title":"Hippo signaling: Bridging the gap between cancer and neurodegenerative disorders","volume":"16","author":"Gogia","year":"2021","journal-title":"Neural Regen. Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:44:23Z","timestamp":1760168663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":114,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123479"],"URL":"https:\/\/doi.org\/10.3390\/cells10123479","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]}}}