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

303 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

Fingerprint

Dive into the research topics of 'Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1'. Together they form a unique fingerprint.

Cite this