{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:38:16Z","timestamp":1780072696344,"version":"3.54.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["819526"],"award-info":[{"award-number":["819526"]}],"id":[{"id":"10.13039\/100019180","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":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Complex perceptual discrimination is supported by tau\u2010vulnerable regions of the medial temporal lobe (MTL); notably the perirhinal cortex. This research tests whether there is a gene\u2010dose effect of apolipoprotein E (APOE) e4 on perceptual discrimination in mid\u2010life.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Three hundred and thirteen adults (45\u201365 years; grouped by APOE e4 gene\u2010dose (142 APOE33, 135 APOE34, 36 APOE44)) completed a Greebles \u201codd\u2010one\u2010out\u201d task.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>APOE44 carriers were significantly less accurate in their perceptual judgments than APOE33 and APOE34 individuals. There was a significant Age x APOE e4 gene\u2010dose interaction in response speed, with the slope of age\u2010related slowing increasing stepwise with the number of e4 alleles carried. Estimates suggest high\u2010risk individuals are quicker than the APOE33 control group until age 54, but slower thereafter.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Perceptual disadvantages specific to APOE44 individuals suggest this high\u2010risk group show compromised MTL function by mid\u2010life, potentially through accelerated tau\u2010aggregation. Task performance in APOE34 carriers is relatively preserved in mid\u2010life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>APOE44 carriers show impaired perceptual discrimination in mid\u2010age.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>APOE34 carriers show preserved perceptual discrimination in mid\u2010age.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Age\u2010related slowing of perceptual judgments increases with APOE e4 gene\u2010dose.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Perceptual discrimination tasks may be a valuable early marker of AD risk.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70246","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:11:14Z","timestamp":1749726674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perceptual discrimination of complex objects: Apolipoprotein E e4 gene\u2010dose effects in mid\u2010life"],"prefix":"10.1002","volume":"21","author":[{"given":"Claire","family":"Lancaster","sequence":"first","affiliation":[{"name":"School of Psychology University of Sussex  Brighton UK"},{"name":"Current address: Brighton &amp; Sussex Medical School University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Berens","sequence":"additional","affiliation":[{"name":"School of Psychology University of Sussex  Brighton 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