Association of Aβ40-positive Senile Plaques with Microglial Cells in the Brains of Patients with Alzheimer's Disease and in Non-demented Aged Individuals

To gain insight into the role of microglia in the formation of senile plaques (SP), especially in the generation of the two major molecular species of amyloid β protein (Aβ) with different carboxyl (C)-termini, Aβ40 and Aβ42(43), we conducted double immunolabelling studies on tissue sections from the brains of Alzheimer's disease (AD) and non-demented aged individuals using antibodies to the C-termini of Aβ and ferritin, a marker for microglia. All SP were Aβ42(43)-positive in AD as well as in non-demented individuals, only a proportion of which were Aβ40-positive. Both in AD and in non-demented individuals, approximately 2/3 of the Aβ40-positive SP were typical SP with amyloid cores, these being almost invariably associated with microglia. Aβ40-positive, uncored SP were also frequently associated with microglia (mean, 74%), whereas only 24% of Aβ40-negative, uncored SP contained microglia. These results suggest that microglia may play a role in the maturation of SP, especially in the generation of Aβ40.