Expression of macrophage colony-stimulating factor receptor is increased in the A beta PPV717F transgenic mouse model of Alzheimer's disease

Inflammation is an important neuropathological change in Alzheimer's diseas e (AD). However, the pathophysiological factors that initiate and maintain the inflammatory response in AD are unknown, We examined A beta PPV717F tra nsgenic mice, which show numerous brain amyloid-beta (A beta) deposits, for expression of the macrophage colony-stimulating factor (M-CSF) and its rec eptor (M-CSFR). M-CSF is increased in the brain. in AD and dramatically aug ments the effects of A beta on cultured microglia, A beta PPV717F animals 1 2 months of age showed large numbers of microglia strongly labeled with an M-CSFR antibody near A beta deposits. M-CSFR mRNA and protein levels were a lso increased in brain homogenates from A beta PPV717F animals. Dystrophic neurites and astroglia showed no M-CSFR labeling in the transgenic animals. A M-CSF antibody decorated neuritic structures near hippocampal A beta dep osits in transgenic animals. M-CSF mRNA was also increased in A beta PPV717 F animals in. comparison with wild-type controls. Simultaneous overexpressi on of M-CSFR and its Ligand in A beta PPV717F animals could result in augme ntation of A beta-induced activation of microglia. Because chronic activati on of microglia is thought to result in neuronal injury, the M-CSF system m ay be a potential target for therapeutic intervention in AD.