In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 25, No. 14 ( 2005-04-06), p. 3621-3627
Abstract:
The ϵ4 allele of apolipoprotein E (ApoE) is a risk factor for Alzheimer's disease (AD), whereas the ϵ2 allele may be relatively protective. Both alleles are risk factors for cerebral amyloid angiopathy (CAA)-related hemorrhages. CAA is associated with degeneration of smooth muscle cells and pericytes. Previously, we described that synthetic amyloid-β 1-40 peptide (Aβ 1-40 ) with the 22 Glu→ Gln “Dutch” mutation caused pericyte death in vitro by a mechanism that involves Aβ fibril-like assembly at the cell surface. It is known that ApoE binds to Aβ and may modify its biological activities. In the present study, we evaluated the effect of ApoE on Aβ-mediated toxicity of cerebrovascular cells. We observed that cultured cells with an ϵ4/ϵ4 genotype were more vulnerable to Aβ than cultures with an ϵ3/ϵ3 or ϵ3/ϵ4 genotype. The one cell culture with the ϵ2/ϵ3 genotype was relatively resistant to Aβ compared with other cultures. Furthermore, we observed a dose-dependent protective effect of native ApoE against Aβ-mediated toxicity of cerebrovascular cells and, in addition, ApoE ϵ2/ϵ3 cells secreted more ApoE protein compared with cells with other ApoE genotypes, in particular, compared with ϵ4/ϵ4 cells. Thus, the disparity between ApoE genotype and Aβ-mediated toxicity might be related to differences in the cellular capacity to secrete ApoE. The present data suggest that one mechanism by which ApoE may alter the risk for AD is a genotype-dependent regulation of Aβ cytotoxicity, possibly via variations in its secretion levels, whereby extracellular ApoE may bind to Aβ and thereby modify Aβ-mediated cell death.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4213-04.2005
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2005
detail.hit.zdb_id:
1475274-8
SSG:
12
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