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.