J. Davissalinas et We. Vannostrand, AMYLOID BETA-PROTEIN AGGREGATION NULLIFIES ITS PATHOLOGICAL PROPERTIES IN CULTURED CEREBROVASCULAR SMOOTH-MUSCLE CELLS, The Journal of biological chemistry, 270(36), 1995, pp. 20887-20890
Alzheimer's disease and related disorders are characterized by deposit
ion of aggregated amyloid beta-protein (A beta) and accompanying patho
logic changes in the neuropil and in the walls of cerebral blood vesse
ls. A beta induces neurotoxicity in vitro, and this effect is markedly
enhanced when the peptide is preaggregated. Recently, we reported tha
t freshly solubilized A beta(1-42) can induce cellular degeneration an
d a striking increase in the levels of cellular amyloid beta-protein p
recursor 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 pr
esent 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 mechanis
ms for A beta-induced cytotoxicity exist for cultured neurons and cere
brovascular smooth muscle cells, supporting that different processes m
ay be involved in the parenchymal and cerebrovascular pathology of Alz
heimer's disease and related disorders.