Spatial relationships between astrocytes and classical plaque components

Abstract

Four biopsies of the brain cortex of patients with Alzheimer's disease were used for ultrastructural studies. Three-dimensional reconstruction and morphometric studies of three classical plaques were carried out to determine the distribution of the astrocytes and their processes, and spatial relationships between astrocytes and plaque components. Morphologic and morphometric studies showed marked ultrastructural changes in the astrocytes located in the vicinity of the plaque. Proliferating processes of the two or three astrocytes nearest to the plaque become part of the plaque. Processes of hypertrophic astrocytes touch neighboring vessels, neurons, and amyloid deposits. The volume of the peripheral amyloid deposits in the classical plaques examined exceeds the volume of the amyloid star by about 26%. Amyloid of the classical plaque periphery appears as amyloid wisps. Most amyloid wisps are isolated between astrocytic processes proliferating and penetrating into the plaque. Proliferation and penetration of astrocytic processes into the plaque lead to fragmentation of amyloid deposits and their dispersion. Reduction in the size of amyloid wisps isolated between astrocytic processes toward the plaque periphery and changes in the morphology of amyloid fibers in this plaque region suggest that astrocytes participate in gradual degradation of at least part of the amyloid fibers.