ROLE OF MICROGLIA IN SENILE PLAQUE-FORMATION

To assess the role of microglial cells in senile plaque (SP) formation , we examined the density and distribution of microglia in the tempora l neocortex of three groups of nondemented individuals, chosen to repr esent sequential stages of SP formation (no SP, n = 14; diffuse plaque s (DP) only, n = 12; both DP and neuritic plaques (NP), n = 14) and pa tients with Alzheimer's disease (AD, n = 11). The mean density of micr oglia was significantly greater in the AD group. In nondemented indivi duals, the presence of NP but not DP was associated with an increased number of microglial cells. Most NP (91%) were focally associated with microglial cells. DP less commonly contained microglia, however, indi viduals with some NP had microglia within a greater proportion of thei r DP (47%) than did those with only DP (19%). These findings suggest t hat: (a) microglia are not involved in the formation of DP; (b) the pr esence of NP is associated with both an overall increase in microglia and the focal aggregation of cells around NP; (c) microglia may be loc ally involved in the conversion of DP into NP. This final point repres ents the most significant aspect of this study, providing the first qu antitative evidence to support a specific role for microglia in the fo rmation of NP from DP.