{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:46:04Z","timestamp":1785415564746,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,29]]},"group-title":"Neuroscience","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 HL059658"],"award-info":[{"award-number":["R01 HL059658"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01 NS136808"],"award-info":[{"award-number":["R01 NS136808"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"award":["K01 AG083732"],"award-info":[{"award-number":["K01 AG083732"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Poor sleep quality and reduced sleep duration are associated with Alzheimer\u2019s disease (AD)-related \u03b2-amyloid (A\u03b2) pathologies. We conducted two studies of sleep\/wake, activity and body temperature in\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice, a strain that exhibits three mutations in the human\n                  <jats:italic>App<\/jats:italic>\n                  gene associated with elevated risk for early onset AD. First,\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice were compared to wildtype (WT) littermates at 14-18 and 18-22 months of age and, at both ages, were found to exhibit more Wake and less NREM and REM sleep than WT littermates. This long wake\/short sleep phenotype was evident during the dark phase at 14-18 months but occurred in both the light and dark phases at 18-22 months.\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice had fewer short (&lt;60 sec) and more long (&gt;260 sec) Wake bouts and were hyperactive at 18-22 months, which undoubtedly contributed to the increased Wake\/reduced sleep. Despite this reduced sleep phenotype,\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice were no sleepier than WT mice and the sleep homeostat was functional in both strains. In the second study, sex differences in these parameters were assessed at 18-24 months. Reduced sleep was evident in both sexes of\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice but was clearly more evident in females. Wake and REM sleep bout durations were longer in both sexes of\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice than in WT littermates. EEG spectral power during NREM sleep was reduced in female\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice between 4.88-10.50 Hz compared to WT mice whereas, during REM sleep, both male and female\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice exhibited reduced spectral power in the theta range. These results suggest that A\u03b2 deposition may impair state transition mechanism(s) in\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice and demonstrate that, as in human AD patients, the long wake\/short sleep phenotype was more evident in female\n                  <jats:italic>App<\/jats:italic>\n                  <jats:sup>NL-G-F<\/jats:sup>\n                  mice, thus supporting the use of this strain as a model to investigate interventions that mitigate AD burden during early disease stages.\n                <\/jats:p>","DOI":"10.64898\/2025.12.29.696818","type":"posted-content","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T23:00:14Z","timestamp":1767049214000},"source":"Crossref","is-referenced-by-count":0,"title":["Long Wake\/Short Sleep Bouts and Hyperactivity with Advanced Age in a Mouse Model of Early Onset Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Ryan K.","family":"Tisdale","sequence":"first","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, 94025 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, 94025 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R.","family":"Miller","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease, San Francisco, CA, 94158 USA"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, 94158 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, 94025 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunmee","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, 94025 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shin","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease, San Francisco, CA, 94158 USA"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, 94158 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Allocca","sequence":"additional","affiliation":[{"name":"Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia"},{"name":"Somnivore Pty. Ltd., Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge J.","family":"Palop","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease, San Francisco, CA, 94158 USA"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, 94158 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-0094","authenticated-orcid":false,"given":"Thomas S.","family":"Kilduff","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, 94025 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