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Studies have shown that exercise can significantly improve AD autophagy abnormalities, but the mechanism underlying this phenomenon remains unclear. APN not only has an important regulatory effect on AD autophagy abnormalities, but also is affected by exercise. Therefore, this study aims to reveal the pathway by which exercise regulates abnormal autophagy in AD using the APN\u2013AdipoR1 signaling pathway as an entry point. The results of the study showed that APP\/PS1 double transgenic AD model mice (24 weeks) showed decreased AdipoR1 levels in the brain, abnormal autophagy, increased A\u03b2 deposition, and increased cell apoptosis, and dendritic spines and cognitive function were reduced. Twelve weeks of aerobic exercise enhanced lysosomes and alleviated abnormal autophagy by activating the AdipoR1\/AMPK\/TFEB signaling pathway in the brains of AD mice, thereby alleviating A\u03b2 deposition and its associated AD-like abnormalities. These findings suggest that the AdipoR1 plays an important role in aerobic exercise\u2019s alleviation of abnormal autophagy in AD brain cells and alleviation of AD-like lesions.<\/jats:p>","DOI":"10.3390\/ijms23179921","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"9921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP\/PS1 Mice by Upregulating AdipoR1 Levels"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-2243","authenticated-orcid":false,"given":"Ye","family":"Jian","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunling","family":"Yuan","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialun","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Lei","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-3670","authenticated-orcid":false,"given":"Wenfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"},{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. 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