Journal
MOLECULAR PSYCHIATRY
Volume 23, Issue 9, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2017.204
Keywords
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Funding
- National Natural Science Foundation of China (NSFC) [81701043, 81625007, 81622015]
- Canadian Institutes of Health Research (CIHR) [TAD-117948]
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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.
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