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This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates A\u03b2 pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a \u201cp-STAT3\u2013APH1\u2013\u03b3-secretase\u201d signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.<\/jats:p>","DOI":"10.1126\/sciadv.ado1855","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T13:59:32Z","timestamp":1719583172000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":42,"title":["TGR5 deficiency in excitatory neurons ameliorates Alzheimer\u2019s pathology by regulating APP processing"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4173-0648","authenticated-orcid":true,"given":"Chenli","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4945-1894","authenticated-orcid":true,"given":"Liangjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-5848","authenticated-orcid":true,"given":"Wenting","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erqu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Can","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiyu","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7339-6286","authenticated-orcid":true,"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350122, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-5848","authenticated-orcid":true,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Anesthesiology, First Affiliated Hospital, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China."},{"name":"Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350122, China."},{"name":"Institute of Neuroscience, Fujian Medical University, Fuzhou, Fujian, 350122, China."},{"name":"The Key Laboratory of Neural and Vascular Biology, Ministry of Education, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21653"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003012"},{"key":"e_1_3_2_4_2","first-page":"416","article-title":"A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models","volume":"26","author":"van Lengerich B.","year":"2023","unstructured":"B. van Lengerich, L. 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