{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:36:15Z","timestamp":1787495775767,"version":"build-2736575974"},"reference-count":75,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["5R01AG054517"],"award-info":[{"award-number":["5R01AG054517"]}],"id":[{"id":"10.13039\/100000049","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":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Circadian rhythm disruption is an early symptom of Alzheimer's disease (AD), though it remains unclear how the light\u2010dark (LD) cycle and the central circadian clock in the suprachiasmatic nucleus (SCN) influence AD pathobiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We disrupted the SCN clock via deletion of\n                      <jats:italic>Bmal1<\/jats:italic>\n                      in GABAergic neurons (VGAT\u2010iCre;\n                      <jats:italic>Bmal1<\/jats:italic>\n                      KO), crossed to the 5xFAD amyloid\u2010beta (A\u03b2)\u00a0model, and raised mice under LD or constant dark (DD) conditions. We examined circadian rhythms, sleep, A\u03b2 plaques, and phospho\u2010tau (p\u2010tau) pathology, and gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>VGAT\u2010Bmal1 knockout (KO) mice showed weakened rhythms in LD and arrhythmicity in DD conditions. LD conditions promoted A\u03b2 plaque accumulation in 5xFAD mice, while VGAT\u2010Bmal1 deletion reduced amyloid precursor protein (APP) cleavage, A\u03b2 plaque accumulation, and peri\u2010plaque p\u2010tau, and induced extracellular matrix (ECM) gene expression in LD, but not DD, conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>In 5xFAD mice, LD cycles interact with the central circadian clock to reinforce A\u03b2 deposition, while central clock disruption or constant darkness unexpectedly mitigate plaque pathology.<\/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>5xFAD mice accumulate more A\u03b2 plaque pathology when raised under standard LD conditions than when raised in DD conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>VGAT\u2010Bmal1 KO eliminates locomotor rhythms in DD conditions and weakens locomotor, sleep, and transcriptional rhythms in LD conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>VGAT\u2010Bmal1 KO; 5xFAD mice aged in LD conditions accumulated less total A\u03b2 plaque and peri\u2010plaque p\u2010tau than their Cre\u2212 littermates. VGAT\u2010Bmal1 KO had no effect onplaque pathology in mice aged in constant darkness.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Amyloid precursor protein carboxy terminal fragments (APP\u2010CTFs) were suppressed in VGAT\u2010Bmal1 KO mice under LD conditions, suggesting reduced A\u03b2 production.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Transcriptomic analysis shows induction of AEBP1 in VGAT\u2010Bmal1 KO, which regulates ECM genes and has been associated with AD pathology in humans.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70885","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:53:37Z","timestamp":1762858417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circadian rhythms and the light\u2010dark cycle interact to regulate amyloid\u2010beta plaque accumulation and tau phosphorylation in 5xFAD mice"],"prefix":"10.1002","volume":"21","author":[{"given":"Melvin W.","family":"King","sequence":"first","affiliation":[{"name":"Department of Neurology and Center on Biological Rhythms and Sleep Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie M.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center on Biological Rhythms and Sleep Washington University School of Medicine  St. Louis Missouri 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