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Neuroscience. 1994 Nov;63(2):517-31.

Beta-amyloid-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer's disease.

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1
Department of Psychobiology, University of California, Irvine 92717-4550.

Abstract

One neuropathological characteristic of Alzheimer's disease is an abundance 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 immunohistochemical analyses of Alzheimer brain tissue. We report that beta-amyloid peptides, in an aggregation-dependent manner, rapidly induce a reactive phenotype in cultured rat astrocytes. Reactive morphological changes are accompanied by increased immunoreactivities for glial fibrillary acidic protein and basic fibroblast growth factor. Although toxic to other types of central nervous system cells, aggregated beta-amyloid peptides do not significantly decrease astrocyte viability. Rather, the processes of cultured astrocytes envelop aggregated deposits of beta-amyloid peptide. In Alzheimer brain, the processes of reactive astrocytes were also observed to engulf beta-amyloid deposits. Similar to the 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 immunoreactivities for glial fibrillary acidic protein and basic fibroblast growth factor. These data suggest that beta-amyloid which has assembled into beta-sheet fibrils significantly contributes to the reactive astrocytosis characteristic of Alzheimer's disease. Thus, in addition to its hypothesized direct effects on neuronal viability, beta-amyloid may also influence disease progression indirectly via reactive astrocytosis.

PMID:
7891862
[Indexed for MEDLINE]

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