Amyloid β protein deposition and neuron loss in osteopetrotic (op/op) mice

Formation of senile plaques (SPs) by amyloid β (Aβ) protein is a neuropathological change which characterizes Alzheimer's disease (AD), and Aβ deposition and neuron loss are essential for the pathological cascade of the disease. Although the mechanism of Aβ deposition remains unclear, it has been suggested that clearance of Aβ protein may be impaired in the AD brain. Previous studies demonstrated that microglia were able to remove Aβ by releasing a metalloprotease or by phagocytosis, suggesting that microglia may play an important role in preventing Aβ deposition in the central nervous system (CNS). On the other hand, it was reported that the number of microglia was reduced in osteopetrotic (op/op) toothless mice resulting from the lack of functional macrophage colony-stimulating factor (M-CSF). The present study was thus designed to examine the Aβ deposition and the number of hippocampal neurons in the brain of op/op mice. A number of fibrillar plaques were detected in the cerebral cortex, hippocampus, amygdala and hypothalamus in op/op mice, however, no quantitative evidence of Aβ deposition was observed in normal mice. Moreover, the total number of pyramidal cells in the hippocampal CA1, and CA3 regions was significantly reduced in op/op mice when compared to the controls. These results demonstrate that Aβ deposition influence neuron loss and it may be suspected that expression of SPs may be in part regulated by microglia under physiological conditions.