Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits
Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits
复制标题
血细胞产生的淀粉样蛋白-β 诱发大脑阿尔茨海默型病理和行为缺陷
DOI：
10.1038/s41380-020-0842-1
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发表时间：
2020-07-17
影响因子：
11
通讯作者：
Wang, Yan-Jiang
中科院分区：
文献类型：
--
作者：
Sun, Hao-Lun;Chen, Si-Han;Wang, Yan-Jiang
It is traditionally believed that cerebral amyloid-beta (A beta) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce A beta. The role of peripherally produced A beta in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced A beta to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human A beta in the blood, and caused AD phenotypes including A beta plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood A beta levels, and alleviated brain A beta burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced A beta plays a significant role in AD pathogenesis, and the elimination of peripheral production of A beta can decrease brain A beta deposition and represents a novel therapeutic approach for AD.
