title: Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model.
abstract: We have recently shown that the ability of microglia to effectively fight off aggregated beta-amyloid plaque formation and cognitive loss in transgenic mouse models of Alzheimer's disease (Tg-AD), is augmented in response to T-cell-based immunization, using glatiramer acetate (GA). The immunization increases incidence of local CD11c+ dendritic-like cells. It is unclear, however, whether these dendritic cells are derived from resident microglia or from the bone marrow. To determine the origin of this dendritic-cell population, we used chimeric mice whose bone marrow-derived cells express a transgene that allows the cells to be specifically ablated by diphtheria toxin. We show here that T-cell-based immunization of these mice, using GA, induced the recruitment of bone marrow-derived dendritic cells. Depletion of the dendritic cells by systemic injection of diphtheria toxin resulted in significantly increased formation of amyloid plaques. Thus, recruitment of bone marrow-derived dendritic cells evidently plays a role in reducing plaque formation in a mouse model of Alzheimer's disease.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Butovsky
authors.forename: Gilad
authors.initials: G
authors.lastname: Kunis
authors.forename: Maya
authors.initials: M
authors.lastname: Koronyo-Hamaoui
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D016026:Bone Marrow Transplantation; D039521:CD11c Antigen / Q000378:metabolism; D002452:Cell Count; D002678:Chimera / Q000235:genetics; D003713:Dendritic Cells / Q000637:transplantation*; D005838:Genotype; D000068717:Glatiramer Acetate; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000473:pathology*
chemical_list: D039521:CD11c Antigen; D010455:Peptides; D000068717:Glatiramer Acetate