Origin and turnover of microglial cells in fibrillar plaques of APPsw transgenic mice.

Activated microglial cells are an integral component of fibrillar plaques in brains of subjects with Alzheimer's disease (AD) and in brains of transgenic mice overexpressing amyloidogenic fragments of human amyloid precursor protein (APP). The aim of this ultrastructural study of fibrillar plaques was to characterize the origin of microglial cells involved in cored plaque formation. Computer-aided three-dimensional reconstruction of plaques and microvessels in APPsw transgenic mice shows perivascular development of cored plaques. Perivascular location of almost all examined plaques and the infiltration at the interface between vessels and plaques with cells of monocyte/microglia lineage indicates that plaques are formed by inflammatory cells of blood origin. The increase in the number of microglial cells from 1 or 2 in an early plaque to more than 100 in a several-month-old plaque does not result in plaque degradation, but is associated with amyloid core growth and progression of neuronal degeneration, and suggests that recruitment of inflammatory cells of blood origin sustains plaque growth. Infiltration of the plaque with cells of blood origin and degeneration of 10-46% of inflammatory cells in large plaques, which is especially frequent at the interface between capillary wall and plaque, suggest their accelerated turnover.