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Despite recent documentation of transcellular mitochondrial transfer, its role in the pathogenesis of AD remains unclear. In this study, we report an impairment of mitochondrial quality within the astrocytes and neurons of adult 5\u2009\u00d7\u2009FAD mice. Following treatment with mitochondria isolated from aged astrocytes induced by exposure to amyloid protein or extended cultivation, cultured neurons exhibited an excessive generation of reactive oxygen species and underwent neurite atrophy. Notably, aerobic exercise enhanced mitochondrial quality by upregulating CD38 within hippocampal astrocytes of 5\u2009\u00d7\u2009FAD mice. Conversely, the knockdown of CD38 diminished astrocytic\u2013neuronal mitochondrial transfer, thereby abolishing the ameliorative effects of aerobic exercise on neuronal oxidative stress, \u03b2\u2010amyloid plaque deposition, and cognitive dysfunction in 5\u2009\u00d7\u2009FAD mice. These findings unveil an unexpected mechanism through which aerobic exercise facilitates the transference of healthy mitochondria from astrocytes to neurons, thus countering the AD\u2010like progression.<\/jats:p>","DOI":"10.1111\/bpa.13316","type":"journal-article","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T02:54:28Z","timestamp":1729997668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease"],"prefix":"10.1111","volume":"35","author":[{"given":"Jiachen","family":"Cai","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration Nanjing Medical University  Nanjing China"},{"name":"Nanjing Brain Hospital Affiliated to Nanjing Medical University  Nanjing 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