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 disease (AD). However, the pathophysiological factors that initiate and maintain the inflammatory response in AD are unknown, We examined A beta PPV717F transgenic mice, which show numerous brain amyloid-beta (A beta) deposits, for expression of the macrophage colony-stimulating factor (M-CSF) and its receptor (M-CSFR). M-CSF is increased in the brain. in AD and dramatically augments the effects of A beta on cultured microglia, A beta PPV717F animals 12 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 also 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 deposits in transgenic animals. M-CSF mRNA was also increased in A beta PPV717F animals in. comparison with wild-type controls. Simultaneous overexpression of M-CSFR and its Ligand in A beta PPV717F animals could result in augmentation of A beta-induced activation of microglia. Because chronic activation of microglia is thought to result in neuronal injury, the M-CSF system may be a potential target for therapeutic intervention in AD.