{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:55:49Z","timestamp":1780736149177,"version":"3.54.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2015\/24699-9"],"award-info":[{"award-number":["2015\/24699-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.<\/jats:p>","DOI":"10.1093\/gerona\/glae023","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T09:25:27Z","timestamp":1704965127000},"source":"Crossref","is-referenced-by-count":7,"title":["Changes in Expression of Key Genes in Alzheimer\u2019s Disease: A Specific Brain Tissue Change"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-2257","authenticated-orcid":false,"given":"Lucas Trevizani","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Department of Biomedicine, University Center of the Integrated Faculties of Ourinhos (Unifio) , Ourinhos, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-6663","authenticated-orcid":false,"given":"Roger Willian","family":"de Labio","sequence":"additional","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-826X","authenticated-orcid":false,"given":"M\u00f4nica Pezenatto","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-6989","authenticated-orcid":false,"given":"Bruno Mari","family":"Fredi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6901-9082","authenticated-orcid":false,"given":"Eduardo Federighi","family":"Baisi Chagas","sequence":"additional","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Department of Physical Education, University of Marilia (Unimar) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-0164","authenticated-orcid":false,"given":"Elizabeth Suchi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Federal University of S\u00e3o Paulo (Unifesp) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-2736","authenticated-orcid":false,"given":"Gustavo","family":"Turecki","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Human Genetics, and Neurology & Neurosurgery, Bell Canada Brain Bank (Douglas Mental Health University Institute) , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-1033","authenticated-orcid":false,"given":"Mar\u00edlia de Arruda Cardoso","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Federal University of S\u00e3o Paulo (Unifesp) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4373-7742","authenticated-orcid":false,"given":"Spencer Luiz Marques","family":"Pay\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Genetics, Marilia Medical School (Famema) , Marilia, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"2026041420072036900_CIT0001","first-page":"735","article-title":"\u03b2-Secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE","volume-title":"Science.","author":"Vassar","year":"1999"},{"key":"2026041420072036900_CIT0002","first-page":"5789","article-title":"Comprehensive review on Alzheimer\u2019 s disease","volume-title":"Molecules.","author":"Breijyeh","year":"2020"},{"key":"2026041420072036900_CIT0003","first-page":"125","article-title":"New approaches for the treatment of Alzheimer\u2019s disease","volume-title":"Bioorganic Med Chem Lett","author":"Fish","year":"2019"},{"key":"2026041420072036900_CIT0004","first-page":"1","article-title":"Structural biology of presenilin 1 complexes","volume-title":"Mol Neurodegener.","author":"Li","year":"2014"},{"key":"2026041420072036900_CIT0005","first-page":"823","article-title":"Specificity of presenilin-1- and presenilin-2-dependent \u03b3-secretases towards substrate processing","volume-title":"J Cell Mol Med.","author":"Stanga","year":"2018"},{"key":"2026041420072036900_CIT0006","first-page":"325","article-title":"The complex role of apolipoprotein E in Alzheimer\u2019s disease: An overview and update","volume-title":"J Mol Neurosci.","author":"Mahoney-Sanchez","year":"2016"},{"key":"2026041420072036900_CIT0007","first-page":"1297","article-title":"Understanding the role of ApoE fragments in Alzheimer\u2019s disease","volume-title":"Neurochem Res.","author":"Mu\u00f1oz","year":"2019"},{"key":"2026041420072036900_CIT0008","first-page":"347","article-title":"Apolipoprotein E, receptors, and modulation of Alzheimer\u2019s disease","volume-title":"Biol Psychiatry.","author":"Zhao","year":"2018"},{"key":"2026041420072036900_CIT0009","first-page":"68","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume-title":"Lancet Neurol.","author":"Serrano-Pozo","year":"2021"},{"key":"2026041420072036900_CIT0010","first-page":"760","article-title":"Change in INSR, APBA2 and IDE gene expressions in brains of Alzheimer\u2019s disease patients","volume-title":"Curr Alzheimer Res.","author":"da Costa","year":"2017"},{"key":"2026041420072036900_CIT0011","first-page":"1","article-title":"Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures","volume-title":"BMC Genomics.","author":"Sutcliffe","year":"2003"},{"key":"2026041420072036900_CIT0012","first-page":"2798","article-title":"Epigenome-wide association study in peripheral tissues highlights DNA methylation profiles associated with episodic memory performance in humans","volume-title":"Biomedicines","author":"Sommerer","year":"2022"},{"key":"2026041420072036900_CIT0013","first-page":"146","article-title":"Promoter characterization and genomic organization of the human X11\u03b2 gene APBA2","volume-title":"Neuroreport.","author":"Hao","year":"2012"},{"key":"2026041420072036900_CIT0014","first-page":"101544","article-title":"Biomarkers used in Alzheimer\u2019s disease diagnosis, treatment, and prevention","volume-title":"Ageing Res Rev.","author":"Mahaman","year":"2022"},{"key":"2026041420072036900_CIT0015","first-page":"1888","article-title":"Single-cell RNA sequencing reveals B cell-related molecular biomarkers for Alzheimer\u2019s disease","volume-title":"Exp Mol Med.","author":"Xiong","year":"2021"},{"key":"2026041420072036900_CIT0016","first-page":"8435","article-title":"Association between LRP1 C766T polymorphism and Alzheimer\u2019 s disease susceptibility: a meta- analysis","volume-title":"Sci Rep.","author":"Wang","year":"2017"},{"key":"2026041420072036900_CIT0017","first-page":"5809","article-title":"Trafficking in Alzheimer\u2019s disease: Modulation of APP transport and processing by the transmembrane proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin","volume-title":"Mol Neurobiol","author":"Eggert","year":"2018"},{"key":"2026041420072036900_CIT0018","first-page":"1267","article-title":"Role of LRP1 in the pathogenesis of Alzheimer\u2019s disease: Evidence from clinical and preclinical studies","volume-title":"J Lipid Res.","author":"Shinohara","year":"2017"},{"key":"2026041420072036900_CIT0019","first-page":"26","article-title":"Insulin resistance in Alzheimer\u2019s disease","volume-title":"Front Neurosci.","author":"Ferreira","year":"2018"},{"key":"2026041420072036900_CIT0020","first-page":"49","article-title":"Insulin-degrading enzyme in the fight against Alzheimer\u2019s disease","volume-title":"Trends Pharmacol Sci.","author":"Kurochkin","year":"2018"},{"key":"2026041420072036900_CIT0021","first-page":"227","article-title":"Diabetes mellitus","volume-title":"Adv Exp Med Biol.","author":"Ohyagi","year":"2019"},{"key":"2026041420072036900_CIT0022","first-page":"554","article-title":"Multiple functions of insulin-degrading enzyme: A metabolic crosslight","volume-title":"Crit Rev Biochem Mol Biol.","author":"Tundo","year":"2017"},{"key":"2026041420072036900_CIT0023","first-page":"333","article-title":"The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention","volume-title":"Neurochem Int.","author":"Sheldon","year":"2007"},{"key":"2026041420072036900_CIT0024","first-page":"2866","article-title":"Natural oligomers of the Alzheimer amyloid- protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway","volume-title":"J Neurosci.","author":"Shankar","year":"2007"},{"key":"2026041420072036900_CIT0025","first-page":"757","article-title":"PSEN1 and PSEN2 gene expression in Alzheimer\u2019s disease brain: A new approach","volume-title":"J Alzheimers Dis","author":"de Labio","year":"2014"},{"key":"2026041420072036900_CIT0026","first-page":"182","article-title":"CDK5 and MAPT gene expression in Alzheimer\u2019s disease brain samples","volume-title":"Curr Alzheimer Res.","author":"Fukasawa","year":"2017"},{"key":"2026041420072036900_CIT0027","first-page":"2953","article-title":"CDK10, CDK11, FOXO1, and FOXO3 gene expression in Alzheimer\u2019s disease encephalic samples","volume-title":"Cell Mol Neurobiol.","author":"Fredi","year":"2023"},{"key":"2026041420072036900_CIT0028","first-page":"931","article-title":"New Alzheimer\u2019s disease locus on chromosome 8","volume-title":"J Med Genet.","author":"Giedraitis","year":"2006"},{"key":"2026041420072036900_CIT0029","first-page":"e64457","article-title":"The causal role of auditory cortex in auditory working memory","volume-title":"Elife","author":"Yu","year":"2021"},{"key":"2026041420072036900_CIT0030","first-page":"151","article-title":"Consensus paper: The cerebellum\u2019s role in movement and cognition","volume-title":"Cerebellum","author":"Koziol","year":"2014"},{"key":"2026041420072036900_CIT0031","first-page":"37","article-title":"The cerebellum in Alzheimer\u2019s disease: Evaluating its role in cognitive decline","volume-title":"Brain.","author":"Jacobs","year":"2018"},{"key":"2026041420072036900_CIT0032","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2018.00396","article-title":"The emerging role of altered cerebellar synaptic processing in Alzheimer\u2019s disease","volume-title":"FrontAging Neurosci","author":"Hoxha","year":"2018"},{"key":"2026041420072036900_CIT0033","first-page":"1","article-title":"Comparative profiling of cortical gene expression in Alzheimer\u2019s disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation","volume-title":"Sci Rep.","author":"Castillo","year":"2017"},{"key":"2026041420072036900_CIT0034","first-page":"215","article-title":"A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer\u2019s disease","volume-title":"Alzheimers Dement","author":"Xu","year":"2018"},{"key":"2026041420072036900_CIT0035","first-page":"1","article-title":"Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation","volume-title":"Sci Rep.","author":"Bergstr\u00f6m","year":"2016"},{"key":"2026041420072036900_CIT0036","first-page":"77","article-title":"MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer\u2019s disease in vivo and in vitro","volume-title":"Acta Biochim Biophys Sin","author":"Ren","year":"2021"},{"key":"2026041420072036900_CIT0037","first-page":"324","article-title":"Alzheimer\u2019s disease, \u03b2-amyloid, glutamate, NMDA receptors and memantine - searching for the connections","volume-title":"Br J Pharmacol.","author":"Danysz","year":"2012"},{"key":"2026041420072036900_CIT0038","first-page":"21362","article-title":"Tumor necrosis factor-\u03b1 induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner","volume-title":"J Biol Chem.","author":"Takeuchi","year":"2006"},{"key":"2026041420072036900_CIT0039","first-page":"102331","article-title":"Astrocyte energy and neurotransmitter metabolism in Alzheimer\u2019s disease: Integration of the glutamate\/GABA-glutamine cycle","volume-title":"Prog Neurobiol.","author":"Andersen","year":"2022"},{"key":"2026041420072036900_CIT0040","first-page":"788","article-title":"Soluble oligomers of amyloid \u03b2 protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake","volume-title":"Neuron.","author":"Li","year":"2009"},{"issue":"6","key":"2026041420072036900_CIT0041","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1139\/jpn.0956","article-title":"Expression profiles of schizophrenia susceptibility genes during human prefrontal cortical development","volume":"34","author":"Choi","year":"2009","journal-title":"J Psychiatry Neurosci."},{"key":"2026041420072036900_CIT0042","first-page":"287","article-title":"Association analysis of GRIN2B, encoding N-methyl-D-aspartate receptor 2B subunit, and Alzheimer\u2019s disease","volume-title":"Dement Geriatr Cogn Disord.","author":"Seripa","year":"2008"},{"key":"2026041420072036900_CIT0043","first-page":"559","article-title":"Cholesterol as a causative agent in Alzheimer disease: A debatable hypothesis","volume-title":"J Neurochem.","author":"Wood","year":"2014"},{"key":"2026041420072036900_CIT0044","first-page":"94","article-title":"Low-density lipoprotein receptor-related protein 1: A physiological A\u03b2 homeostatic mechanism with multiple therapeutic opportunities","volume-title":"Pharmacol Ther.","author":"Sagare","year":"2012"},{"key":"2026041420072036900_CIT0045","first-page":"1101","article-title":"Alzheimer\u2019s disease is type 3 diabetes-evidence reviewed","volume-title":"J Diabetes Sci Technol.","author":"De La Monte","year":"2008"},{"key":"2026041420072036900_CIT0046","first-page":"841","article-title":"Oxidative stress kinase activation and impaired insulin receptor signaling precede overt Alzheimer\u2019s disease neuropathology","volume-title":"J Alzheimers Dis","author":"Shen","year":"2022"},{"key":"2026041420072036900_CIT0047","first-page":"531","article-title":"Alzheimer\u2019s disease and insulin resistance: Translating basic science into clinical applications","volume-title":"J Clin Invest.","author":"De Felice","year":"2013"},{"key":"2026041420072036900_CIT0048","first-page":"5202","article-title":"Obesity as a risk factor for dementia and Alzheimer\u2019s disease: The role of leptin","volume-title":"Int J Mol Sci.","author":"Flores-Cordero","year":"2022"},{"key":"2026041420072036900_CIT0049","first-page":"1486","article-title":"Insulin resistance, cognition, and Alzheimer disease","volume-title":"Obesity","author":"Kim","year":"2023"},{"key":"2026041420072036900_CIT0050","first-page":"17494","article-title":"Defining early changes in Alzheimer\u2019s disease from RNA sequencing of brain regions differentially affected by pathology","volume-title":"Sci Rep.","author":"Guennewig","year":"2021"}],"container-title":["The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/advance-article-pdf\/doi\/10.1093\/gerona\/glae023\/56410105\/glae023.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/79\/5\/glae023\/57331510\/glae023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/79\/5\/glae023\/57331510\/glae023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:14:30Z","timestamp":1776212070000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/doi\/10.1093\/gerona\/glae023\/7588735"}},"subtitle":[],"editor":[{"given":"Gustavo","family":"Duque","sequence":"additional","affiliation":[{"name":"(Biological Sciences Section)"}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/glae023","relation":{},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,1]]},"published":{"date-parts":[[2024,1,24]]},"article-number":"glae023"}}