{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T01:16:11Z","timestamp":1782522971256,"version":"3.54.5"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"671","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,11,16]]},"abstract":"<jats:p>\n            The apolipoprotein E (\n            <jats:italic>APOE<\/jats:italic>\n            ) \u03b54 allele is strongly linked with cerebral \u03b2-amyloidosis, but its relationship with tauopathy is less established. We investigated the relationship between\n            <jats:italic>APOE<\/jats:italic>\n            \u03b54 carrier status, regional amyloid-\u03b2 (A\u03b2), magnetic resonance imaging (MRI) volumetrics, tau positron emission tomography (PET),\n            <jats:italic>APOE<\/jats:italic>\n            messenger RNA (mRNA) expression maps, and cerebrospinal fluid phosphorylated tau (CSF ptau\n            <jats:sub>181<\/jats:sub>\n            ). Three hundred fifty participants underwent imaging, and 270 had ptau\n            <jats:sub>181<\/jats:sub>\n            . We used computational models to evaluate the main effect of\n            <jats:italic>APOE<\/jats:italic>\n            \u03b54 carrier status on regional neuroimaging values and then the interaction of \u03b54 status and global A\u03b2 on regional tau PET and brain volumes as well as CSF ptau\n            <jats:sub>181<\/jats:sub>\n            . Separately, we also examined the additional interactive influence of sex. We found that, for the same degree of A\u03b2 burden,\n            <jats:italic>APOE<\/jats:italic>\n            \u03b54 carriers showed greater tau PET signal relative to noncarriers in temporal regions, but no interaction was present for MRI volumes or CSF ptau\n            <jats:sub>181<\/jats:sub>\n            . This potentiation of tau aggregation irrespective of sex occurred in brain regions with high\n            <jats:italic>APOE<\/jats:italic>\n            mRNA expression, suggesting local vulnerabilities to tauopathy. There were greater effects of\n            <jats:italic>APOE<\/jats:italic>\n            genotype in females, although the interactive sex effects did not strongly mirror mRNA expression. Pathology is not homogeneously expressed throughout the brain but mirrors underlying biological patterns such as gene expression.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abl7646","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T18:58:11Z","timestamp":1668625091000},"source":"Crossref","is-referenced-by-count":30,"title":["APOE \u03b54 genotype, amyloid-\u03b2, and sex interact to predict tau in regions of high APOE mRNA expression"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-0840","authenticated-orcid":true,"given":"Aylin","family":"Dincer","sequence":"first","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA."},{"name":"Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, 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