{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:46:43Z","timestamp":1783637203349,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201020\u2010683875"],"award-info":[{"award-number":["AARG\u201020\u2010683875"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>We tested sex\u2010dependent associations of variation in the <jats:italic>SNAP\u201025<\/jats:italic> gene, which encodes a presynaptic protein involved in hippocampal plasticity and memory, on cognitive and Alzheimer's disease (AD) neuroimaging outcomes in clinically normal adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were genotyped for SNAP\u201025 rs1051312 (T\u00a0&gt;\u00a0C; SNAP\u201025 expression: C\u2010allele\u00a0&gt;\u00a0T\/T). In a discovery cohort (<jats:italic>N<\/jats:italic>\u00a0=\u00a0311), we tested the sex by <jats:italic>SNAP\u201025<\/jats:italic> variant interaction on cognition, A\u03b2\u2010PET positivity, and temporal lobe volumes. Cognitive models were replicated in an independent cohort (<jats:italic>N<\/jats:italic>\u00a0=\u00a082).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the discovery cohort, C\u2010allele carriers exhibited better verbal memory and language, lower A\u03b2\u2010PET positivity rates, and larger temporal volumes than T\/T homozygotes among females, but not males. Larger temporal volumes related to better verbal memory only in C\u2010carrier females. The female\u2010specific C\u2010allele verbal memory advantage was evidenced in the replication cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In females, genetic variation in SNAP\u201025 is associated with resistance to amyloid plaque formation and may support verbal memory through fortification of temporal lobe architecture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The <jats:italic>SNAP\u201025<\/jats:italic> rs1051312 (T\u00a0&gt;\u00a0C) C\u2010allele results in higher basal SNAP\u201025 expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>C\u2010allele carriers had better verbal memory in clinically normal women, but not men.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Female C\u2010carriers had higher temporal lobe volumes, which predicted verbal memory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Female C\u2010carriers also exhibited the lowest rates of amyloid\u2010beta PET positivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The <jats:italic>SNAP\u201025<\/jats:italic> gene may influence female\u2010specific resistance to Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12989","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T14:59:15Z","timestamp":1676732355000},"page":"3448-3457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex\u2010specific effects of <i>SNAP\u201025<\/i> genotype on verbal memory and Alzheimer's disease biomarkers in clinically normal older adults"],"prefix":"10.1002","volume":"19","author":[{"given":"Rowan","family":"Saloner","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences University of California  San Francisco 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