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Amyloid burden and microglial density were quantified with whole\u2010brain light\u2010sheet microscopy. CSF1R\u2010mediated microglial depletion explored effects of microglia on sleep loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Amyloid plaques caused non\u2013rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with cortical hyperexcitability, network desynchrony, and microglial expansion extending beyond plaque\u2010bearing regions into thalamocortical and white matter networks governing sleep\u2013wake dynamics. Microglial depletion restored\u00a0&gt;\u00a02\u00a0hours of sleep per day without altering amyloid burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Microglia are a causal, reversible driver of amyloid\u2010associated sleep loss, positioning sleep and EEG\u2010based metrics as sensitive biomarkers of presymptomatic AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71579","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T03:44:29Z","timestamp":1780890269000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Nicholas J.","family":"Constantino","sequence":"first","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Neuroscience University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley E.","family":"Irmen","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Lanning","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra M.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clair C.","family":"Ashley","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin M.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Alzheimer's Disease Research Center Wake Forest University School of Medicine  Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan M.","family":"Neary","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Rubinow","sequence":"additional","affiliation":[{"name":"LifeCanvas Technologies  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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