Amyloid beta-protein aggregation nullifies its pathologic properties in cultured cerebrovascular smooth muscle cells

Alzheimer's disease and related disorders are characterized by deposition of aggregated amyloid beta-protein (A beta) and accompanying pathologic changes in the neuropil and in the walls of cerebral blood vessels. A beta induces neurotoxicity in vitro, and this effect is markedly enhanced when the peptide is preaggregated. Recently, we reported that freshly solubilized A beta 1-42 can induce cellular degeneration and a striking increase in the levels of cellular amyloid beta-protein precursor and soluble A beta 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 beta 1-42 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 beta-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.