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Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies

文献类型：期刊论文

作者Tan, J.10; Wang, J.1,2; Shen, L-L1,2; Huang, Z-L3,4; Zhang, K.5,6; Liu, Y-H1,2; Zeng, F.1,2; Liu, J-H7,8; Sun, H-L1,2; Zhuang, Z-Q1,2
刊名MOLECULAR PSYCHIATRY
出版日期2018-09-01
卷号23期号:9页码:9
ISSN号1359-4184
DOI10.1038/mp.2017.204
通讯作者Song, W.(weihong@mail.ubc.ca) ; Wang, Y-J(yanjiang_wang@tmmu.edu.cn)
英文摘要The amyloid-beta protein (A beta) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that A beta deposited in the brain originates from the brain tissue itself. However, A beta is generated in both brain and peripheral tissues. Whether circulating A beta contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human A beta originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and A beta plaques after a 12-month period of parabiosis. AD-type pathologies related to the A beta accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived A beta can enter the brain, form the A beta-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting A beta metabolism in both the brain and the periphery.
WOS关键词PRECURSOR PROTEIN ; SECRETASE ACTIVITY ; APOLIPOPROTEIN-E ; BRAIN-BARRIER ; PEPTIDE ; ANGIOPATHY ; CLEARANCE ; INDUCTION ; DENSITY ; TISSUES
资助项目National Natural Science Foundation of China (NSFC)[81701043] ; National Natural Science Foundation of China (NSFC)[81625007] ; National Natural Science Foundation of China (NSFC)[81622015] ; Canadian Institutes of Health Research (CIHR)[TAD-117948]
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000450892900008
资助机构National Natural Science Foundation of China (NSFC) ; National Natural Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; Canadian Institutes of Health Research (CIHR) ; National Natural Science Foundation of China (NSFC) ; National Natural Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; Canadian Institutes of Health Research (CIHR) ; National Natural Science Foundation of China (NSFC) ; National Natural Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; Canadian Institutes of Health Research (CIHR) ; National Natural Science Foundation of China (NSFC) ; National Natural Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; Canadian Institutes of Health Research (CIHR)
源URL[http://cas-ir.dicp.ac.cn/handle/321008/166550]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Song, W.; Wang, Y-J
作者单位1.Third Mil Med Univ, Daping Hosp, Dept Neurol, 10 Changjiang Branch Rd, Chongqing 400042, Peoples R China
2.Third Mil Med Univ, Daping Hosp, Ctr Clin Neurosci, Chongqing, Peoples R China
3.Chongqing Med Univ, Childrens Hosp, Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China
4.Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Translat Med Res Cognit Dev & L, Chongqing, Peoples R China
5.Third Mil Med Univ, Brain Res Ctr, Chongqing, Peoples R China
6.Third Mil Med Univ, State Key Lab Trauma Burns & Combined Injury, Chongqing, Peoples R China
7.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
8.Univ Chinese Acad Sci, Beijing, Peoples R China
9.Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Neurosci, Neuroimmunol Lab, Tampa, FL USA
10.Univ S Florida, Morsani Coll Med, Dept Psychiat & Behav Neurosci, Silver Child Dev Ctr,Rashid Lab Dev Neurobiol, Tampa, FL USA
推荐引用方式
GB/T 7714		 Tan, J.,Wang, J.,Shen, L-L,et al. Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies[J]. MOLECULAR PSYCHIATRY,2018,23(9):9.
APA Tan, J..,Wang, J..,Shen, L-L.,Huang, Z-L.,Zhang, K..,...&Jin, W-S.(2018).Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies.MOLECULAR PSYCHIATRY,23(9),9.
MLA Tan, J.,et al."Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies".MOLECULAR PSYCHIATRY 23.9(2018):9.

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来源：大连化学物理研究所

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