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We propose that autophagic impairment is associated with chronic sleep disruption and examine how sleep loss and stress influence disease development, including having impacts on proteostasis, cognition, and neural circuitry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We sleep\u2010disrupted 6\u2010month\u2010old APP\n                      <jats:sup>NL\u2010G\u2010F<\/jats:sup>\n                      mice for 2\u00a0weeks and behaviorally assessed sleep recovery, nesting, stress, and cognition. Subsequently, we analyzed markers of Alzheimer's pathology, stress, neuroinflammation, and proteostasis in hippocampal and subcortical brain regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Sleep\u2010deprived mice had altered sleep\u2010related behaviors, increased stress, and signs of disease\u2010acceleration including sex\u2010dependent neurodegeneration, proteinopathy, and changes to autophagy and the neuroinflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Chronic sleep disruption accelerates the pathological cascade of Alzheimer's, including cognitive impairment and Alzheimer's pathology in a sex\u2010dependent manner. This work enhances our understanding of the sleep\u2013stress\u2013Alzheimer's relationship, including sex\u2010based differences, and may point to a novel therapeutic avenue to limit Alzheimer's progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71099","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:54:16Z","timestamp":1769835256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex\u2010specific acceleration of Alzheimer's pathogenesis by chronic sleep\u2010deprivation"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-7991","authenticated-orcid":false,"given":"Darcy","family":"Wear","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Brain Health Imaging Centre Centre for Addiction and Mental Health  Toronto Ontario 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