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Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)\/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, A\u03b2 clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2\u2009~\u20093\u00a0months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13195-024-01392-0","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T05:02:24Z","timestamp":1706331744000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A nonhuman primate model with Alzheimer\u2019s disease-like pathology induced by hippocampal overexpression of human tau"],"prefix":"10.1186","volume":"16","author":[{"given":"Zhouquan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpeng","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanggong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"1392_CR1","doi-asserted-by":"publisher","unstructured":"No authors listed. 2021 Alzheimer's disease facts and figures. 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(IACUC No. YXSW-2021\u2013002) and Jinan University (IACUC No. 20210806\u201303) and were in full compliance with the \u201cGuide for the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Science (est. 2006)\u201d and \u201cThe use of nonhuman primates in research of the Institute of Laboratory Animal Science (est. 2006)\u201d to ensure the safety of personnel and animal welfare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Gong Chen is a co-founder of NeuExcell Therapeutics Inc. The other authors have no conflicts of interest to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22"}}