BETA-AMYLOID-INDUCED CHANGES IN CULTURED ASTROCYTES PARALLEL REACTIVEASTROCYTOSIS ASSOCIATED WITH SENILE PLAQUES IN ALZHEIMERS-DISEASE

One neuropathological characteristic of Alzheimer's disease is an abun dance of reactive astrocytes, particularly in association with senile plaques. Neither the factor(s) responsible for initiating the reactive astrocytosis nor the effects of this event on disease progression are known. We investigated the possibility that beta-amyloid protein, the primary constituent of plaques, contributes to reactive astrocytosis by comparing results derived from both culture studies and immunohisto chemical analyses of Alzheimer brain tissue. We report that beta-amylo id peptides, in an aggregation-dependent manner, rapidly induce a reac tive phenotype in cultured rat astrocytes. Reactive morphological chan ges are accompanied by increased immunoreactivities for glial fibrilla ry acidic protein and basic fibroblast growth factor. Although toxic t o other types of central nervous system cells, aggregated beta-amyloid peptides do not significantly decrease astrocyte viability. Rather, t he processes of cultured astrocytes envelop aggregated deposits of bet a-amyloid peptide. In Alzheimer brain, the processes of reactive astro cytes were also observed to engulf beta-amyloid deposits. Similar to t he in vitro findings, the astrocytic response was associated only with beta-amyloid plaques exhibiting an aggregated structure. Further, the plaque-associated reactive astrocytes showed enhanced immunoreactivit ies for glial fibrillary acidic protein and basic fibroblast growth fa ctor. These data suggest that beta-amyloid which has assembled into be ta-sheet fibrils significantly contributes to the reactive astrocytosi s characteristic of Alzheimer's disease. Thus, in addition to its hypo thesized direct effects on neuronal viability, beta-amyloid may also i nfluence disease progression indirectly via reactive astrocytosis.