{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:14:21Z","timestamp":1783415661133,"version":"3.54.6"},"reference-count":25,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101499"],"award-info":[{"award-number":["82101499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of Chongqing, China","award":["CSTB2022NSCQ-MSX1100"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1100"]}]},{"name":"Natural Science Foundation of Shigatse, China","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic hypoxia has been acknowledged as a significant risk factor for Alzheimer's disease (AD), yet the impact of high-altitude hypoxia on AD pathogenesis remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to investigate the effects of chronic high-altitude hypoxia on cognitive function and AD-related pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cross-sectional cohort comprising 186 high-altitude migrants (HAM) and 378 high-altitude natives (HAN) was recruited for a preliminary assessment. We further conducted 101 HAM, 135 HAN, and 66 low-altitude controls (LA) for plasma biomarkers research. Plasma A\u03b2\n                      <jats:sub>40<\/jats:sub>\n                      , A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      , and T-tau levels were quantified by SIMOA. In parallel, APP\/PS1 mice were exposed to hypobaric hypoxia (simulated at 5,500\u2005m) or normoxia for 30 days, followed by behavioral tests, brain immunohistochemistry, and transcriptomic\/proteomic analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HAM subjects exhibited significant deficits in Montreal Cognitive Assessment scores and delayed recall subscores compared to LA controls, with both measures showing a positive correlation with peripheral oxygen saturation (SpO\u2082). Notably, HAN showed preserved memory despite lower overall cognitive scores. Plasma levels of amyloid-\u03b2 (A\u03b2)\n                      <jats:sub>40<\/jats:sub>\n                      , A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      , and A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      \/A\u03b2\n                      <jats:sub>40<\/jats:sub>\n                      ratio were significantly lower in both HAM and HAN groups compared to the LA group. In mice, chronic hypoxia exacerbated hippocampal A\u03b2 deposition and induced spatial memory decline. Multi-omics analyses revealed the upregulation of oxidative stress and neuroinflammatory pathways and identified S100A8\/A9 as a potential key mediator in hypoxia-accelerated AD pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that chronic high-altitude hypoxia contributes to cognitive decline and AD-related pathological changes, likely mediated by A\u03b2 burden and oxidative stress. High-altitude hypoxia might be an important environmental risk factor for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261431844","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T13:53:01Z","timestamp":1774014781000},"page":"422-432","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic high-altitude hypoxia exacerbates cognitive impairment and Alzheimer\u2019s disease pathology"],"prefix":"10.1177","volume":"111","author":[{"given":"Jie-Ming","family":"Jian","sequence":"first","affiliation":[{"name":"920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Daping Hospital, Army Medical University"},{"name":"Chongqing Key Laboratory of Ageing and Brain 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