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Enhancing gamma\u2010aminobutyric acid\u2010ergic (GABAergic) signaling can restore sleep. Unbiased computational analysis identified zolpidem as high\u2010affinity GABA receptor modulator facilitating chloride transport that could slow AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Zolpidem's effects on sleep and Alzheimer's progression were evaluated in young APP\/PS1 (amyloid precursor protein\/presenilin 1) mice. Sleep was monitored with electroencephalography\/electromyography (EEG\/EMG) telemetry. Wide\u2010field imaging with voltage\u2010sensitive dyes (VSDs) was used to track sleep\u2010dependent brain rhythms. Multiphoton microscopy allowed assessments of amyloid plaque load and basal neuronal calcium levels. Behavioral assays were used to measure memory and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Zolpidem restored NREM sleep and rescued sleep\u2010dependent brain rhythm, slow oscillation. Zolpidem administration reduced cortical amyloid plaque burden, mitigated neuronal calcium overload, and enhanced sleep\u2010dependent contextual recall without adverse effects on locomotion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Zolpidem effectively decreased amyloid in young APP\/PS1 mice. This supports zolpidem's therapeutic promise as an intervention strategy at early stages of AD.<\/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>Zolpidem treatment improves non\u2013rapid eye movement (NREM) sleep stability and reduces sleep fragmentation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Zolpidem restores slow oscillation in young APP\/PS1 (amyloid precursor protein\/presenilin 1) mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Zolpidem treatment reduces amyloid plaque burden and calcium overload in neurons.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Zolpidem\u2010treated mice show improved sleep\u2010dependent memory consolidation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Sleep rhythm enhancement shows promise for Alzheimer's therapy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71175","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:00:22Z","timestamp":1773226822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Zolpidem restores sleep and decreases amyloid in a mouse model"],"prefix":"10.1002","volume":"22","author":[{"given":"Lu","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology MassGeneral Institute of Neurodegenerative Diseases Mass General Brigham and Harvard Medical School  Charlestown Massachusetts USA"},{"name":"Department of Neurology The Affiliated Hospital of Xuzhou Medical University Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-9695","authenticated-orcid":false,"given":"Shinya","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"Department of Neurology MassGeneral Institute of Neurodegenerative Diseases Mass General Brigham and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tri H.","family":"Doan","sequence":"additional","affiliation":[{"name":"Department of Neurology MassGeneral Institute of Neurodegenerative Diseases Mass General Brigham and Harvard Medical School  Charlestown Massachusetts 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