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Tissues from dorsolateral prefrontal cortex were examined to identify 8425 proteins. <jats:italic>Post mortem<\/jats:italic> pathological assessment used immunohistochemistry to obtain amyloid beta (A\u03b2) load and tau tangle density.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In separate models, <jats:italic>APOE<\/jats:italic> \u025b4 was associated with 18 proteins, which were associated with A\u03b2 and tau tangles. Examining the proteins in a single model identified Netrin\u20101 and secreted frizzled\u2010related protein 1 (SFRP1) as the two proteins linking <jats:italic>APOE<\/jats:italic> \u025b4 with A\u03b2 with the largest effect sizes and Netrin\u20101 and testican\u20103 linking <jats:italic>APOE<\/jats:italic> \u025b4 with tau tangles.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>We identified Netrin\u20101, SFRP1, and testican\u20103 as the most promising proteins that link <jats:italic>APOE<\/jats:italic> \u025b4 with A\u03b2 and tau tangles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Of 8425 proteins extracted from prefrontal cortex, 18 were related to <jats:italic>APOE<\/jats:italic> \u025b4.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The 18 proteins were also related to amyloid beta (A\u03b2) and tau.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The 18 proteins were more related to <jats:italic>APOE<\/jats:italic> \u025b4 than other AD genetic risk variants.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Netrin\u20101 and secreted frizzled\u2010related protein 1 were the two most promising proteins linking <jats:italic>APOE<\/jats:italic> \u025b4 with A\u03b2.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Netrin\u20101 and testican\u20103 were two most promising proteins linking <jats:italic>APOE<\/jats:italic> \u025b4 with tau.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13867","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:31:47Z","timestamp":1718008307000},"page":"4499-4511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Proteins linking <i>APOE<\/i> \u025b4 with Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Shahram","family":"Oveisgharan","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":"Katia","family":"de Paiva Lopes","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":"Shinya","family":"Tasaki","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":"Yanling","family":"Wang","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilas","family":"Menon","sequence":"additional","affiliation":[{"name":"Center for Translational and Computational Neuroimmunology Department of Neurology &amp; 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