An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments

doi:10.1038/s41422-021-00582-x

	An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments
	Pang, Keliang 7,9,10; Jiang, Richeng 1,2; Zhang, Wei 5,6; Yang, Zhengyi 11; Li, Lin-Lin 3,4; Shimozawa, Makoto 1; Tambaro, Simone 1; Mayer, Johanna 1; Zhang, Baogui 11; Li, Man 5,6
刊名	CELL RESEARCH
	2021-11-17
页码	19
ISSN号	1001-0602
DOI	10.1038/s41422-021-00582-x
通讯作者	Guo, Wei(wguo@tsinghua.edu.cn) ; Lu, Bai(bai_lu@tsinghua.edu.cn)
英文摘要	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.
资助项目	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]
WOS关键词	AMYLOID-PRECURSOR-PROTEIN ; TRANSGENIC MICE ; MOUSE MODELS ; SEX ; ISOFORMS ; MUTATION ; MEMORY ; AGE ; NEURODEGENERATION ; NEUROPATHOLOGY
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000719692600001
资助机构	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
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/46464]
专题	自动化研究所_脑网络组研究中心
通讯作者	Guo, Wei; Lu, Bai
作者单位	1.Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden 2.First Hosp Jilin Univ, Dept Otorhinolaryngol Head & Neck Surg, Changchun, Peoples R China 3.Univ CAS, Sch Future Technol, Res Ctr Brain Inspired Intelligence, Inst Automat,Natl Lab Pattern Recognit, Shanghai, Peoples R China 4.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China 5.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China 6.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China 7.Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing Tiantan Hosp, Beijing, Peoples R China 8.Karolinska Univ Hosp, Theme Aging, Huddinge, Sweden 9.Res Inst Tsinghua Univ Shenzhen, R&D Ctr Diag & Treatment Major Brain Dis, Shenzhen, Guangdong, Peoples R China 10.Tsinghua Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Pharmaceut Sci, IDG McGovern Inst Brain Res, Beijing, Peoples R China
推荐引用方式 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.