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Mol Psychiatry. 2017 Oct 31. doi: 10.1038/mp.2017.204. [Epub ahead of print]

Blood-derived amyloid-β protein induces Alzheimer's disease pathologies.

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Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
Ministry of Education Key Laboratory of Child Development and Disorders and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Brain Research Center and State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
University of Chinese Academy of Sciences, Beijing, China.
Neuroimmunology Laboratory, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
School of Pharmacy and Medical Sciences and Sansom Institute, University of South Australia, Adelaide, SA, Australia.
Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada.


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.Molecular Psychiatry advance online publication, 31 October 2017; doi:10.1038/mp.2017.204.


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