期刊
NEUROBIOLOGY OF AGING
卷 101, 期 -, 页码 94-108出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2021.01.001
关键词
BCG; Immune; Microglia; Macrophage; Alzheimer's disease
资金
- National Natural Science Foundation of China [81801058]
- Foundation of Medical Science and Technology Research of Guangdong Province [A2018157]
- Fundamental Research Funds for the Central Universities [19ykpy169]
The study suggests that A beta immunotherapy may exacerbate vascular A beta-associated pathology in Alzheimer's disease, whereas BCG treatment can improve this condition and enhance the efficacy of A beta vaccine. BCG treatment not only enhances the phagocytosis of A beta but also alleviates pathological changes by recruiting protective monocytes.
Despite effective clearance of parenchymal amyloid-beta (A beta) in patients with Alzheimer's disease, A beta immunotherapy exacerbates the vascular A beta (VA beta)-associated pathology in the brain. We have previously shown that BCG immunization facilitates protective monocyte recruitment to the brain of APP/PS1 mice. Here, we confirmed that the 4A beta 1-15 vaccine exacerbates VA beta deposits in this model, which coincides with a decrease in the number of cerebrovascular endothelial cells and pericytes, infiltration of neutrophils into the brain, and induction of cerebral microhemorrhage. Moreover, combined 4A beta 1-15/BCG treatment abrogates the development of the VA beta-associated pathology. In addition, BCG treatment is required for the upregulation of interleukin-10 in the brain. Notably, BCG treatment selectively enhances A beta phagocytosis by recruited macrophages. Furthermore, combined 4A beta 1-15/BCG treatment is more effective than 4A beta 1-15 monotherapy in synaptic preservation and the enhancement of the learning efficiency. Overall, our study suggests that the combination of A beta-targeted therapy with an immunomodulatory strategy may improve the efficacy of A beta vaccine in Alzheimer's disease. (C) 2021 Elsevier Inc. All rights reserved.
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