Association of A beta 40-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 beta protein (A beta) with different carboxyl (C)-termini, A beta 40 and A beta 42(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 A beta and ferritin, a marker for microglia. All SP were A beta 42(43)-positive in AD as well as in non-demented individuals, only a proportion of which were A beta 40-positive. Both in AD and in non-demented individuals, approximately 2/3 of the A beta 40-positive SP were typical SP with amyloid cores, these being almost invariably associated with microglia. A beta 40-positive, uncored SP were also frequently associated with microglia (mean, 74%), whereas only 24% of A beta 40-negative, uncored SP contained microglia. These results suggest that microglia may play a role in the maturation of SP, especially in the generation of A beta 40.