期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2006
卷号：103
期号：31
页码：11784-11789
DOI：10.1073/pnas.0604681103
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Alzheimer's disease (AD) is characterized by plaque formation, neuronal loss, and cognitive decline. The functions of the local and systemic immune response in this disease are still controversial. Using AD double-transgenic (APP/PS1) mice, we show that a T cell-based vaccination with glatiramer acetate, given according to a specific regimen, resulted in decreased plaque formation and induction of neurogenesis. It also reduced cognitive decline, assessed by performance in a Morris water maze. The vaccination apparently exerted its effect by causing a phenotype switch in brain microglia to dendritic-like (CD11c) cells producing insulin-like growth factor 1. In vitro findings showed that microglia activated by aggregated [beta]-amyloid, and characterized as CD11b+/CD11c-/MHC class II-/TNF-{alpha}+ cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b+/CD11c+/MHC class II+/TNF-{alpha}- microglia, a phenotype induced by IL-4, counteracted the adverse [beta]-amyloid-induced effect. These results suggest that dendritic-like microglia, by facilitating the necessary adjustment, might contribute significantly to the brain's resistance to AD and argue against the use of antiinflammatory drugs.
