| An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments | |
Pang, Keliang1,2,3; Jiang, Richeng4,5; Zhang, Wei6,7; Yang, Zhengyi8 ; Li, Lin-Lin9,10; Shimozawa, Makoto4; Tambaro, Simone4; Mayer, Johanna4; Zhang, Baogui8; Li, Man6,7; Wang, Jiesi6,7; Liu, Hang1,2,3; Yang, Ailing1; Chen, Xi9,10; Liu, Jiazheng9,10; Winblad, Bengt4,11; Han, Hua9,10; Jiang, Tianzi8; Wang, Weiwen6,7; Nilsson, Per4; Guo, Wei1,2,3; Lu, Bai1,2,3
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| Source Publication | CELL RESEARCH
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| ISSN | 1001-0602 |
| 2021-11-17 | |
| Pages | 19 |
| Corresponding Author | Guo, Wei(wguo@tsinghua.edu.cn) ; Lu, Bai(bai_lu@tsinghua.edu.cn) |
| Abstract | A major obstacle in Alzheimer's disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The App knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiar App mutations and humanized A beta sequence knocked into the rat App gene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of A beta plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. This App knock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics. |
| DOI | 10.1038/s41422-021-00582-x |
| WOS Keyword | AMYLOID-PRECURSOR-PROTEIN ; TRANSGENIC MICE ; MOUSE MODELS ; SEX ; ISOFORMS ; MUTATION ; MEMORY ; AGE ; NEURODEGENERATION ; NEUROPATHOLOGY |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | National Key Research and Development Program of China[2017YFE0126500] ; National Natural Science Foundation of China[81861138013] ; National Natural Science Foundation of China[81501105] ; National Natural Science Foundation of China[31730034] ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission[JCYJ20170411152419928] ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission[JCYJ20180508152240368] ; Beijing Municipal Science & Technology Commission[Z151100003915118] ; Strategic Priority Research Program of Chinese Academy of Science[XDB32030200] ; Hallstens forskningsstiftelse ; Swedish Research Council ; Swedish Brain foundation ; Swedish Alzheimer foundation ; Margaretha af Ugglas Foundation ; China Scholarship Council ; H2020-MSCA-ITN-2019[860035] |
| Funding Organization | National Key Research and Development Program of China ; National Natural Science Foundation of China ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission ; Beijing Municipal Science & Technology Commission ; Strategic Priority Research Program of Chinese Academy of Science ; Hallstens forskningsstiftelse ; Swedish Research Council ; Swedish Brain foundation ; Swedish Alzheimer foundation ; Margaretha af Ugglas Foundation ; China Scholarship Council ; H2020-MSCA-ITN-2019 |
| WOS Research Area | Cell Biology |
| WOS Subject | Cell Biology |
| WOS ID | WOS:000719692600001 |
| Publisher | SPRINGERNATURE |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ia.ac.cn/handle/173211/46465 |
| Collection | 类脑智能研究中心_微观重建与智能分析 脑网络组研究 |
| Corresponding Author | Guo, Wei; Lu, Bai |
| Affiliation | 1.Tsinghua Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Pharmaceut Sci, IDG McGovern Inst Brain Res, Beijing, Peoples R China 2.Res Inst Tsinghua Univ Shenzhen, R&D Ctr Diag & Treatment Major Brain Dis, Shenzhen, Guangdong, Peoples R China 3.Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing Tiantan Hosp, Beijing, Peoples R China 4.Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden 5.First Hosp Jilin Univ, Dept Otorhinolaryngol Head & Neck Surg, Changchun, Peoples R China 6.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China 7.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China 8.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing, Peoples R China 9.Univ CAS, Sch Future Technol, Res Ctr Brain Inspired Intelligence, Inst Automat,Natl Lab Pattern Recognit, Shanghai, Peoples R China 10.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China 11.Karolinska Univ Hosp, Theme Aging, Huddinge, Sweden |
| Recommended Citation GB/T 7714 | Pang, Keliang,Jiang, Richeng,Zhang, Wei,et al. An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments[J]. CELL RESEARCH,2021:19. |
| APA | Pang, Keliang.,Jiang, Richeng.,Zhang, Wei.,Yang, Zhengyi.,Li, Lin-Lin.,...&Lu, Bai.(2021).An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments.CELL RESEARCH,19. |
| MLA | Pang, Keliang,et al."An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments".CELL RESEARCH (2021):19. |
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