{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T21:22:05Z","timestamp":1770326525879,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The molecular mechanism underlying Alzheimer's disease (AD) pathologies remains unclear. The brain is extremely sensitive to oxygen deprivation, and brief interruptions in oxygen supply may lead to permanent brain damage. The objective here was to access the red blood cell (RBC) physiological alterations and the changes in blood oxygen saturation of an AD model as well as to explore the possible mechanism underlying these pathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used female <jats:italic>APP<\/jats:italic><jats:sup><jats:italic>swe<\/jats:italic><\/jats:sup><jats:italic>\/PS1<\/jats:italic><jats:sup><jats:italic>\u0394E9<\/jats:italic><\/jats:sup> mice as AD models. Data were collected at the age of 3, 6, and 9\u2009months. In addition to examining classic features of AD, namely cognitive deficiency and A\u03b2 depositions, 24\u2009h blood oxygen saturation was monitored by Plus oximeters in real time. In addition, RBC physiological parameters were measured by blood cell counter using peripheral blood from the epicanthal veins. Furthermore, in the mechanism investigations, the expression of phosphorylated band 3 protein was examined by a series of Western blot analyses, and the levels of soluble A\u03b240 and A\u03b242 on the membrane of RBCs were determined by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that the blood oxygen saturation in the AD mice was significantly reduced as early as at 3\u2009months of age, preceding the neuropathological changes and cognitive impairments. Meanwhile, the expression of phosphorylated band 3 protein and levels of soluble A\u03b240 and A\u03b242 were all elevated in the erythrocytes of the AD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>APP<\/jats:italic><jats:sup><jats:italic>swe<\/jats:italic><\/jats:sup><jats:italic>\/PS1<\/jats:italic><jats:sup><jats:italic>\u0394E9<\/jats:italic><\/jats:sup> mice exhibited decreased oxygen saturation together with reduced RBC counts and hemoglobin concentrations at the early stage, which may aid in the development of predictive markers for AD diagnosis. The increased expression of band 3 protein and elevated A\u03b240 and A\u03b242 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14147","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T07:56:21Z","timestamp":1678262181000},"page":"1889-1897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>APP<sup>swe<\/sup><\/i>\/<i>PS1<sup>\u0394E9<\/sup><\/i> mice exhibit low oxygen saturation and alterations of erythrocytes preceding the neuropathology and cognitive deficiency during Alzheimer's disease"],"prefix":"10.1111","volume":"29","author":[{"given":"Manli","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Neurology, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu China"},{"name":"Chinese Academy of Sciences 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