Alzheimer's disease and related disorders are characterized by deposition of aggregated amyloid -protein (A) and accompanying pathologic changes in the neuropil and in the walls of cerebral blood vessels. A induces neurotoxicity in vitro, and this effect is markedly enhanced when the peptide is preaggregated. Recently, we reported that freshly solubilized A can induce cellular degeneration and a striking increase in the levels of cellular amyloid -protein precursor and soluble A peptide in cultured cerebrovascular smooth muscle cells (Davis-Salinas, J., Saporito-Irwin, S. M., Cotman, C. W., and Van Nostrand, W. E.(1995) J. Neurochem. 65, 931-934). In the present study, we show that preaggregation of A abolishes the ability of the peptide to induce these cellular pathologic responses in these cells in vitro. These findings suggest that distinct mechanisms for A-induced cytotoxicity exist for cultured neurons and cerebrovascular smooth muscle cells, supporting that different processes may be involved in the parenchymal and cerebrovascular pathology of Alzheimer's disease and related disorders.

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