Relationship between apoptosis of neurons and microglia activation in Alzheimer's disease

Abstract

To assess the relationship between microglia activation and apoptosis of neurons, and the significance of activated microglias in the formation and progression of senile plaques in Alzheimer's disease. IL-1alpha and beta-amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain tissue samples from 10 patients with Alzheimer's disease and 4 negative control cases without neurological disease. The number of resting microglias in the brains of Alzheimer's disease patients was similar to that of the control group (P > 0.05), but the number of activated microglias was significant greater in the Alzheimer's disease patients than that of the controls (P < 0.01). The activated microglias displayed altered size and morphology, and was therefore, categorized into three subtypes as primed, enlarged and phagocytic microglias. The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5 +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and 16.75% of all activated microglias respectively. The number of TUNEL positive apoptotic neurons was significantly greater in Alzheimer patients than that in the control group (P < 0.05). There was a close relationship between the apoptosis of neurons and the activation of microglias (P < 0.01). The activated microglias were differentially distributed among four different plaque types in Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques. Hyperplasia and activation of microglias are a common phenomena in AD and may play an important role in its pathogenesis. There is a close relationship between the apoptosis of neurons and activation of microglias. The activation of microglias may play a key pathogenic role in senile plaque formation and progression of Alzheimer disease.