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 1,2,3; Jiang, Richeng 4,5; Zhang, Wei 6,7; Yang, Zhengyi8 ; Li, Lin-Lin9,10 ; Shimozawa, Makoto 4; Tambaro, Simone 4; Mayer, Johanna 4; Zhang, Baogui8 ; Li, Man 6,7; Wang, Jiesi 6,7; Liu, Hang 1,2,3; Yang, Ailing 1; Chen, Xi9,10 ; Liu, Jiazheng 9,10; Winblad, Bengt 4,11; Han, Hua9,10 ; Jiang, Tianzi8 ; Wang, Weiwen 6,7; Nilsson, Per 4; Guo, Wei 1,2,3; Lu, Bai 1,2,3
发表期刊	CELL RESEARCH
ISSN	1001-0602
	2021-11-17
页码	19
通讯作者	Guo, Wei(wguo@tsinghua.edu.cn) ; Lu, Bai(bai_lu@tsinghua.edu.cn)
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.
DOI	10.1038/s41422-021-00582-x
关键词[WOS]	AMYLOID-PRECURSOR-PROTEIN ; TRANSGENIC MICE ; MOUSE MODELS ; SEX ; ISOFORMS ; MUTATION ; MEMORY ; AGE ; NEURODEGENERATION ; NEUROPATHOLOGY
收录类别	SCI
语种	英语
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]
项目资助者	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研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000719692600001
出版者	SPRINGERNATURE
引用统计	被引频次：40[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/46465
专题	脑图谱与类脑智能实验室_微观重建与智能分析脑图谱与类脑智能实验室_脑网络组研究
通讯作者	Guo, Wei; Lu, Bai
作者单位	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
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.