DICP OpenIR
Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies
Bu, X-L1,2; Xiang, Y.1,2; Jin, W-S1,2; 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; Chen, S-H1,2; Yao, X-Q1,2; Giunta, B.9; Shan, Y-C7; Tan, J.10; Chen, X-W5,6; Dong, Z-F3,4; Zhou, H-D1,2; Zhou, X-F11,12; Song, W.13; Wang, Y-J1,2
Corresponding AuthorSong, W.(weihong@mail.ubc.ca) ; Wang, Y-J(yanjiang_wang@tmmu.edu.cn)
Source PublicationMOLECULAR PSYCHIATRY
2018-09-01
ISSN1359-4184
DOI10.1038/mp.2017.204
Volume23Issue:9Pages:9
Funding ProjectNational 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]
Funding OrganizationNational 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)
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
WOS KeywordPRECURSOR PROTEIN ; SECRETASE ACTIVITY ; APOLIPOPROTEIN-E ; BRAIN-BARRIER ; PEPTIDE ; ANGIOPATHY ; CLEARANCE ; INDUCTION ; DENSITY ; TISSUES
AbstractThe 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.
Language英语
Funding OrganizationNational 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)
WOS IDWOS:000450892900008
PublisherNATURE PUBLISHING GROUP
Citation statistics
Cited Times:26[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166551
Collection中国科学院大连化学物理研究所
Corresponding AuthorSong, W.; Wang, Y-J
Affiliation1.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
11.Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia
12.Univ South Australia, Sansom Inst, Adelaide, SA, Australia
13.Univ British Columbia, Dept Psychiat, Townsend Family Labs, Vancouver, BC, Canada
Recommended Citation
GB/T 7714
Bu, X-L,Xiang, Y.,Jin, W-S,et al. Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies[J]. MOLECULAR PSYCHIATRY,2018,23(9):9.
APA Bu, X-L.,Xiang, Y..,Jin, W-S.,Wang, J..,Shen, L-L.,...&Wang, Y-J.(2018).Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies.MOLECULAR PSYCHIATRY,23(9),9.
MLA Bu, X-L,et al."Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies".MOLECULAR PSYCHIATRY 23.9(2018):9.
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