Abstract
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.
Highlights
Alzheimer’s disease (AD)1 is characterized by deposition of the 39 – 42-amino acid amyloid -protein (A) in senile plaques within the neuropil and within the walls of cerebral blood vessels [1,2,3,4]
Senile plaques found in brains of patients with AD and related disorders are composed of insoluble A aggregates [3, 4]
Previous studies have shown that incubation of preaggregated synthetic A peptides with primary rat or human cortical and hippocampal neuronal cultures causes enhanced neurotoxicity compared with freshly solubilized A peptides [33,34,35,36]
Summary
Alzheimer’s disease (AD)1 is characterized by deposition of the 39 – 42-amino acid amyloid -protein (A) in senile plaques within the neuropil and within the walls of cerebral blood vessels [1,2,3,4]. Incubation of A1–42 with HLSM cells caused extensive cellular degeneration accompanied by striking increases in the levels of cellular APP and extracellular, soluble A peptide [32]. Previous studies have shown that incubation of preaggregated synthetic A peptides with primary rat or human cortical and hippocampal neuronal cultures causes enhanced neurotoxicity compared with freshly solubilized A peptides [33,34,35,36].
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