Amyloid β Protein Deposition in Osteopetrotic (op/op) Mice Is Reduced by Injections of Macrophage Colony Stimulating Factor

Abstract

The deposition of amyloid β (Aβ) protein is a neuropathological change that characterizes Alzheimer's disease. Animals with the osteopetrosis (op/op) mutation suffer from a general skeletal sclerosis, a significantly reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF). This study examined the effect that M-CSF injections had on Aβ deposition and microglial cell distribution in the brains of normal and op/op mice. Aβ-positive plaques were detected in the cerebral cortex of op/op mice, but not in normal mice. M-CSF reduced the numbers of Aβ-positive plaques in op/op mice. The microglial cell population was reduced in op/op mice compared with normal mice, and M-CSF increased the numbers to 65.8% of that observed in normal mice. Our results suggest that a clearer understanding of the role that microglial cells play in Aβ deposition may help determine the mechanisms involved in the pathogenesis of Alzheimer's disease.