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.
Davis-Salinas
J
J
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717-4025, USA.
Van Nostrand
W E
WE
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides