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

Abstract

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.