BLOOD DERIVED MICROGLIA CAN REDUCE PLAQUES IN ALZHEIMER’S DISEASE
Microglia, the immune cells of the brain, invade the central nervous system at the time of vascularization via the pia mater, the walls of blood vessels and the tela choroidea. This resident microglia are not effective in removing amyloid plaques in Alzheimer’s disease (AD), a just published on Neuron new work by Simard et al. (Bone Marrow-Derived Microglia Play a Critical Role in Restricting Senile Plaque Formation in Alzheimer’s Disease. Neuron 49, 489-502, 2006) show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of the disease. Most of these cells originate from the bone marrow, and the β-amyloid-40 and β-amyloid-42 isoforms are able to trigger this chemoattraction.
These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous β-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed Simard’s group to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a powerful tool for the elimination of toxic plaques.