The Role of Microglial Cell Subsets in Alzheimers Disease

G.      Naert; S.      Rivest

Abstract

Alzheimer disease (AD) is characterized by a progressive cognitive decline and accumulation of β-amyloid (Aβ) forming senile plaques that are associated with inflammatory molecules and cells. Resident microglia and newly differentiated cells that are derived from the bone marrow are found in the vicinity of Aβ plaques. Although these two types of microglia are not distinguishable by specific markers in the brain, they seem to possess different phenotype and functions. In mouse models of AD, bone marrow-derived microglia (BMDM) have been shown to delay or stop the progression of AD and preventing their recruitment exacerbates the pathology. Transplantation of competent hematopoietic stem cells or their genetic modifications ameliorate cognitive functions, reduce Aβ accumulation and prevent synaptic dysfunctions. Improving the recruitment of genetically-modified BMDM may be considered as a powerful new therapeutic strategy to counteract AD. Here we review the role of microglia subsets in AD and how these cells have a great potential to fight against Aβ accumulation and cognitive impairment.

Keywords: Microglia, Alzheimers disease, CCR2, CX3CR1, Inflammation, Innate immunity, Cytokines, Chemokines