Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model

Eur J Neurosci. 2007 Jul;26(2):413-6. doi: 10.1111/j.1460-9568.2007.05652.x. Epub 2007 Jul 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Animals
  • Bone Marrow Transplantation*
  • CD11c Antigen / metabolism
  • Cell Count
  • Chimera / genetics
  • Dendritic Cells / transplantation*
  • Genotype
  • Glatiramer Acetate
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Peptides / pharmacology
  • Plaque, Amyloid / pathology*

Substances

  • CD11c Antigen
  • Peptides
  • Glatiramer Acetate