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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 β-amyloid, and characterized as CD11b⁺/CD11c⁻/MHC class II⁻/TNF-α⁺ cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b⁺/CD11c⁺/MHC class II⁺/TNF-α …