Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies
Autor: | Brian Giunta, Hao-Lun Sun, Xin-Fu Zhou, Zhang K, Zhifang Dong, Xiang Y, Jun Tan, Lin-Lin Shen, Xiaowei Chen, Shan Yc, Zhen-Qian Zhuang, Hua-Dong Zhou, Jun Wang, Yu-Hui Liu, Fan Zeng, Jiewei Liu, Xian-Le Bu, Ye-Ran Wang, Jin Ws, Xiu-Qing Yao, Huang Zl, Si-Han Chen, Weihong Song |
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Přispěvatelé: | Bu, X-L, Xiang, Y, Jin, W-S, Wang, J, Zhou, X-F, Wang, YJ |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
pathogenesis of Alzheimer’s disease business.industry Parabiosis Transgene Neurodegeneration Long-term potentiation Alzheimer's disease Hippocampal formation medicine.disease Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine Medicine Cerebral amyloid angiopathy amyloid-β protein business Molecular Biology Neuroscience 030217 neurology & neurosurgery Neuroinflammation |
Zdroj: | Molecular Psychiatry. 23:1948-1956 |
ISSN: | 1476-5578 1359-4184 |
Popis: | The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ 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 Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ 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 Aβ can enter the brain, form the Aβ-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 Aβ metabolism in both the brain and the periphery. Refereed/Peer-reviewed |
Databáze: | OpenAIRE |
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