Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1

Oleg Butovsky, Maya Koronyo-Hamaoui, Gilad Kunis, Eran Ophir, Gennady Landa, Hagit Cohen, Michal Schwartz

    Research output: Contribution to journalArticlepeer-review

    313 Scopus citations

    Abstract

    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-/TMF- α+ cells, impeded neurogenesis from adult neural stem/progenitor cells, whereas CD11b+/CD11c+/MHC class II+/TNF-α- microglia, a phenotype induced by IL-4, counteracted the adverse β-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.

    Original languageEnglish
    Pages (from-to)11784-11789
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume103
    Issue number31
    DOIs
    StatePublished - 1 Aug 2006

    Keywords

    • CD11c
    • Immunomodulation
    • Neurodegeneration
    • T cell vaccination
    • β-amyloid

    ASJC Scopus subject areas

    • General

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