{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:40:09Z","timestamp":1792658409120,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"\n Objectives<\/jats:title>\n \n Apolipoprotein\u2009E \u03b54 (\n APOE \u03b54<\/jats:italic>\n ), a robust genetic risk factor for Alzheimer's disease (AD) is associated with functional connectivity deficits and amyloid pathology in brain regions involved in sleep regulation. Thus, alterations in sleep architecture may be one pathway through which\n \u03b54<\/jats:italic>\n contributes to Alzheimer's disease vulnerability. However, sleep architecture characteristics associated with\n APOE \u03b54<\/jats:italic>\n remain poorly characterized.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This cross\u2010sectional study examined associations between\n APOE<\/jats:italic>\n genotype and sleep architecture among adults aged 50\u201385\u2009years enrolled in the Sleep Heart Health Study (N\u2009=\u20093,081).\n APOE<\/jats:italic>\n genotype was classified into\n \u03b54<\/jats:italic>\n heterozygotes,\n \u03b54<\/jats:italic>\n homozygotes,\n \u03b52<\/jats:italic>\n carriers, and\n \u03b53<\/jats:italic>\n homozygotes (reference group). Sleep architecture was defined using macro\u2010level traits (percentage of time spent in in each sleep stage and wake after sleep onset) and micro\u2010level traits (spindle characteristics [power, density, and frequency], odds ratio product [ORP], and arousal index). Associations between\n APOE<\/jats:italic>\n genotype and each sleep metric was evaluated using linear regression.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Macroarchitecture was largely comparable across genotypes. However, substantial differences in micro\u2010level traits were identified, including lower spindle power among\n \u03b5<\/jats:italic>\n 4 homozygotes (\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22122.14,\n p<\/jats:italic>\n \u2009=\u20090.02) and a dose\u2013response decrease in spindle frequency at peak power with each\n \u03b5<\/jats:italic>\n 4 count (\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4 heterozygotes\n <\/jats:sub>\n \u2009=\u2009\u22120.04,\n p<\/jats:italic>\n \u2009=\u20090.04;\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4 homozygote\n <\/jats:sub>\n \u2009=\u2009\u22120.12,\n p<\/jats:italic>\n \u2009=\u20090.065). Both ORP and arousal index decreased in a dose\u2013response pattern with each\n \u03b5<\/jats:italic>\n 4 count (ORP,\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4\u2010heterozygosity\n <\/jats:sub>\n \u2009=\u2009\u22120.03,\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4\u2010homozygosity\n <\/jats:sub>\n \u2009=\u2009\u22120.07, all\n p<\/jats:italic>\n \u2009<\u20090.01; arousal index,\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4\u2010heterozygosity\n <\/jats:sub>\n \u2009=\u2009\u22121.02,\n p<\/jats:italic>\n \u2009=\u20090.006,\n \u03b2<\/jats:italic>\n \n \u03b5<\/jats:italic>\n 4\u2010homozygosity\n <\/jats:sub>\n \u2009=\u2009\u22121.78,\n p<\/jats:italic>\n \u2009=\u20090.07). Between\u2010genotype differences in ORP widened with age. Associations did not vary by sex, race, cognitive status, pTau181, or A\n \u03b2<\/jats:italic>\n 42:40 ratio.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n Abnormal spindle activity observed among\n \u03b5<\/jats:italic>\n 4 carriers may contribute to their elevated Alzheimer's disease risk.\n \u03b54<\/jats:italic>\n carriers also showed less sleep fragmentation, which may reflect diminished arousability or electroencephalogram slowing due to neurodegenerative changes. ANN NEUROL 2026;100:1012\u20131022\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.78312","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:49:25Z","timestamp":1790077765000},"page":"1012-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Investigation of Sleep Macro\u2010 and Microarchitecture by\n \n APOE<\/i>\n <\/scp>\n Genotype"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-8982","authenticated-orcid":false,"given":"Gawon","family":"Cho","sequence":"first","affiliation":[{"name":"Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Chen","sequence":"additional","affiliation":[{"name":"Yale School of Medicine New Haven Connecticut 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