Amyloid β-Protein Induces Its Own Production in Cultured Degenerating Cerebrovascular Smooth Muscle Cells |
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Authors: | Judianne Davis-Salinas Susan M Saporito-Irwin Carl W Cotman William E Van Nostrand |
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Institution: | Departments of Microbiology and Molecular Genetics and; Psychobiology, University of California, Irvine, California, U.S.A. |
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Abstract: | Abstract: The progression of Alzheimer's disease and related disorders involves amyloid β-protein (Aβ) deposition and pathologic changes in the parenchyma as well as cerebral blood vessels. The cerebrovascular Aβ deposits in these disorders are associated with degenerating smooth muscle cells in the vessel wall, which have been shown to express the Aβ precursor (AβPP) and Aβ. Here, we show that Aβ1–42, an abundant cerebrovascular form of Aβ, causes cellular degeneration in cultured human cerebrovascular smooth muscle cells. This stress response is accompanied by a striking increase in the levels of cellular AβPP and soluble Aβ peptide produced in these degenerating cells. These data provide the first experimental evidence that Aβ can potentially contribute to the onset and progression of the cerebrovascular pathology. The present findings suggest that this mechanism may involve a molecular cascade with a novel product-precursor relationship that results in the adverse production and subsequent accumulation of Aβ. |
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Keywords: | Alzheimer's disease Amyloid β-protein Cerebrovascular pathology Smooth muscle cells |
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