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Here, we investigated the changes of Rab5a in 5\u2009\u00d7\u2009FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The total Rab5a and Rab5a\u2010GTP in 5\u2010month\u2010old 5\u2009\u00d7\u2009FAD mice and wild\u2010type mice were detected using WB and IP technologies. 5\u2009\u00d7\u2009FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4\u2009weeks and CRE\/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5\u2009\u00d7\u2009FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic\u2010related and NGF signal\u2010related proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The total Rab5a was unaltered, but Rab5a\u2010GTP increased and the rab5a\u2010positive early endosomes appeared enlarged in the hippocampus of 5\u2009\u00d7\u2009FAD mice. Notably, EA reduced Rab5a\u2010GTP in the hippocampus in the early stage of 5\u2009\u00d7\u2009FAD mice. EA could improve object recognition memory and spatial learning memory by reducing Rab5a activity in the early stage of 5\u2009\u00d7\u2009FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic\u2010related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5\u2009\u00d7\u2009FAD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rab5a hyperactivation is an early pathological manifestation of 5\u2009\u00d7\u2009FAD mice. EA could suppress Rab5a\u2010GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5\u2009\u00d7\u2009FAD mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14743","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T10:44:56Z","timestamp":1716461096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Electroacupuncture regulates Rab5a\u2010mediating <scp>NGF<\/scp> transduction to improve learning and memory ability in the early stage of <scp>AD<\/scp> mice"],"prefix":"10.1111","volume":"30","author":[{"given":"Jianhong","family":"Li","sequence":"first","affiliation":[{"name":"The Institute of Rehabilitation Industry Fujian University of Traditional Chinese Medicine  Fuzhou China"},{"name":"Fujian Key Laboratory of Aptamers Technology 900TH hospital of 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