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As most studies rely on mouse models, we investigated these genes and proteins in the cortical brain tissue of older adults and their role in Alzheimer's disease (AD) and related disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We leveraged protein measurements, single\u2010nuclei, and RNASeq data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) of over 1200 samples for association analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Expression of\u00a0<jats:italic>SPP1<\/jats:italic>\u00a0and its encoded protein osteopontin were associated with faster cognitive decline and greater odds of common neuropathologies. At single\u2010cell resolution,\u00a0 integrin subunit alpha X (<jats:italic>ITGAX<\/jats:italic>) was highly expressed in microglia, where specific subpopulations were associated with AD and cerebral amyloid angiopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The study provides evidence of <jats:italic>SPP1<\/jats:italic>\u00a0and\u00a0<jats:italic>ITGAX<\/jats:italic>\u00a0association with cognitive decline and common neuropathologies identifying a microglial subset associated with disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13474","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T02:55:53Z","timestamp":1695178553000},"page":"525-537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Associations of cortical <i>SPP1<\/i> and <i>ITGAX<\/i> with cognition and common neuropathologies in older adults"],"prefix":"10.1002","volume":"20","author":[{"given":"Katia de Paiva","family":"Lopes","sequence":"first","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and Virology Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Immunology Harvard Medical School  Boston Massachusetts 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Sciences Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Psychiatry, McLean Hospital Harvard Medical School  Belmont Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal Schnaider","family":"Beeri","sequence":"additional","affiliation":[{"name":"Joseph Sagol Neuroscience Center, Sheba Medical Center  Ramat Gan Israel"},{"name":"Department of Psychiatry Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Herbert and Jackeline Krieger Klein Alzheimer's Research Center Rutgers Biomedical and Health Sciences, Rutgers University  New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas T.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer's Disease Research Center, Department of Neurology and Department of Biochemistry Emory University School of Medicine  Atlanta Georgia 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