{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:36:25Z","timestamp":1769124985692,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000988","name":"Helen Bader Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000988","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001272","name":"Northwestern Mutual Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002082","name":"Extendicare Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002082","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":[[2011,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Apolipoprotein E (<jats:italic>APOE<\/jats:italic>) genotypes are associated with variable risk of developing late\u2010onset Alzheimer's disease (LOAD), with <jats:italic>APOE<\/jats:italic> epsilon 4 (<jats:italic>APOE<\/jats:italic> \u025b4) having higher risk. A variable poly\u2010T length polymorphism at rs10524523, within intron 6 of the translocase of the outer mitochondrial membrane (TOMM40) gene, has been shown to influence age of onset in LOAD, with very long (VL) poly\u2010T length associated with earlier disease onset, and short poly\u2010T length associated with later onset. In this study, we tested the hypothesis that brain and cognitive changes suggestive of presymptomatic LOAD may be associated with this <jats:italic>TOMM40<\/jats:italic> polymorphism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Among healthy <jats:italic>APOE<\/jats:italic> \u025b3 homozygous adults (N = 117; mean age, 55 years), we compared those who were homozygous for VL\/VL (n = 35) <jats:italic>TOMM40<\/jats:italic> poly\u2010T lengths (who were presumably at higher risk) with those homozygous for short (S\/S; n = 38) poly\u2010T lengths, as well as those with heterozygous (S\/VL; n = 44) poly\u2010T length polymorphisms, on measures of learning and memory and on structural brain imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The VL\/VL group showed lower performance than the S\/S <jats:italic>TOMM40<\/jats:italic> group on primacy retrieval from a verbal list learning task, a finding which is also seen in early Alzheimer's disease. A dose\u2010dependent increase in the VL <jats:italic>TOMM40<\/jats:italic> polymorphism (from no VL alleles, to S\/VL heterozygous, to VL\/VL homozygous) was associated with decreasing gray matter volume in the ventral posterior cingulate and medial ventral precuneus, a region of the brain affected early in LOAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings among APOE \u025b3\/\u025b3 late middle\u2010aged adults suggest that a subgroup with VL <jats:italic>TOMM40<\/jats:italic> poly\u2010T lengths may be experiencing incipient LOAD\u2010related cognitive and brain changes.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2010.11.012","type":"journal-article","created":{"date-parts":[[2011,7,25]],"date-time":"2011-07-25T22:38:35Z","timestamp":1311633515000},"page":"456-465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["The effect of <i>TOMM40<\/i> poly\u2010T length on gray matter volume and cognition in middle\u2010aged persons with <i>APOE<\/i><b>\u025b<\/b>3\/<b>\u025b<\/b>3 genotype"],"prefix":"10.1002","volume":"7","author":[{"given":"Sterling C.","family":"Johnson","sequence":"first","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI USA"},{"name":"Geriatric Research Education and Clinical Center William S. 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Middleton Memorial Veterans Hospital Madison WI USA"},{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L.","family":"Koscik","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara B.","family":"Bendlin","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center William S. Middleton Memorial Veterans Hospital Madison WI USA"},{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen D.","family":"Roses","sequence":"additional","affiliation":[{"name":"Deane Drug Discovery Institute Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Deane Drug Discovery Institute Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Deane Drug Discovery Institute Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison WI USA"},{"name":"Geriatric Research Education and Clinical Center William S. 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