EARLY ASSOCIATION OF REACTIVE ASTROCYTES WITH SENILE PLAQUES IN ALZHEIMERS-DISEASE

The fibrillar beta-amyloid protein (AP) plaques of Alzheimer's disease (AD) are associated with reactive astrocytes and dystrophic neurites and have been suggested to contribute to neurodegenerative events in t he disease. We recently reported parallel in vitro and in situ finding s, suggesting that the adoption of a reactive phenotype and the coloca lization of astrocytes with plaques in AD may be mediated in large par t by aggregated A beta. Thus, A beta-mediated effects on astrocytes ma y directly affect disease progression by modifying the degenerative pl aque environment. Alternatively, plaque-associated reactive astrocytos is may primarily represent a glial response to the neural injury assoc iated with plaques and not significantly contribute to AD pathology. T o investigate the validity of these two positions, we examined the dif ferential colocalization of reactive astrocytes and dystrophic neurite s with plaques. Hippocampal sections from AD brains-ranging in neuropa thology from mild to severe-were triple-labeled with antibodies recogn izing A beta protein, reactive astrocytes, and dystrophic neurites. We observed not only plaques containing both or neither cell type, but a lso plaques containing (1) reactive astrocytes but not dystrophic neur ites and (2) dystrophic neurites but not reactive astrocytes. The rela tive proportion of plaques colocalized with reactive astrocytes in the absence of dystrophic neurites is relatively high in mild AD but sign ificantly decreases over the course of the disease, suggesting that pl aque-associated astrocytosis may be an early and perhaps contributory event in AD pathology rather than merely a response to neuronal injury . These data underscore the potentially significant contributions of r eactive astrocytosis in modifying the plaque environment in particular and disease progression in general. (C) 1996 Academic Press, Inc.