{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:45:44Z","timestamp":1789436744462,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Decreases in body mass index (BMI) may be early consequences of Alzheimer's disease (AD) pathophysiological changes. Previous research in the UK Biobank estimated that AD\u2010related genes began affecting BMI around age 47. We assessed whether this result could be replicated using longitudinal data in an independent cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using All of Us (AOU) (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0197,619, aged 30+) data, we estimated linear mixed models for associations of\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010scored AD\u2010Genetic Risk Score (AD\u2010GRS) with BMI, stratified by decade of age. We calculated the earliest age at which AD\u2010GRS was associated with differences in BMI using cross\u2010validated models adjusted for demographics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Higher AD\u2010GRS was statistically associated with lower BMI in participants aged 60\u201370 (\n                      <jats:italic>b<\/jats:italic>\n                      \u00a0=\u00a0\u22120.060 [\u22120.113, \u22120.007]). Best fitting models suggested the inverse association of AD\u2010GRS and BMI emerged beginning at ages 47\u201354.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>AD genes accelerate age\u2010related weight loss starting in middle age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Understanding when physiological changes from amyloid pathology begin is key for AD prevention.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings indicate that AD\u2010associated genes accelerate midlife weight loss, starting between 47 and 54 years.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AD prevention research should consider that disease pathology likely begins by middle age.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14598","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:29:32Z","timestamp":1743985772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of genetic risk score for Alzheimer's disease with late\u2010life body mass index in all of us: Evaluating reverse causation"],"prefix":"10.1002","volume":"21","author":[{"given":"Minhyuk","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Buto","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"},{"name":"Department of Epidemiology Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willa D.","family":"Brenowitz","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"},{"name":"Kaiser Permanente Center for Health Research  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"},{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina Zeki Al","family":"Hazzouri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Kezios","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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