title: Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1.
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 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.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Butovsky
authors.forename: Maya
authors.initials: M
authors.lastname: Koronyo-Hamaoui
authors.forename: Gilad
authors.initials: G
authors.lastname: Kunis
authors.forename: Eran
authors.initials: E
authors.lastname: Ophir
authors.forename: Gennady
authors.initials: G
authors.lastname: Landa
authors.forename: Hagit
authors.initials: H
authors.lastname: Cohen
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D005802:Genes, MHC Class II; D000068717:Glatiramer Acetate; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000502:physiology; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D010641:Phenotype; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D039481:CD11b Antigen; D039521:CD11c Antigen; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D010455:Peptides; D053764:Presenilin-1; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000068717:Glatiramer Acetate; D007334:Insulin-Like Growth Factor I