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However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1\/2, and\/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4\/C\/EBP\u03b2 double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1\/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual A\u03b2 aggregation and neurofibrillary tangles formation in the brain validated by A\u03b2 PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4\/C\/EBP\u03b2 mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.<\/jats:p>","DOI":"10.1038\/s41380-024-02565-x","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T10:01:49Z","timestamp":1713952909000},"page":"3040-3055","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Thy1-ApoE4\/C\/EBP\u03b2 double transgenic mice act as a sporadic model with Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1306-6829","authenticated-orcid":false,"given":"Zhengjiang","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiHao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-8154","authenticated-orcid":false,"given":"Keqiang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"2565_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3233\/JAD-2001-3111","volume":"3","author":"DJ Selkoe","year":"2001","unstructured":"Selkoe DJ. 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