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The ß-amyloid peptide in Alzheimer's disease decreases adhesion of vascular muscle cells to the basement membrane

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journal contribution
posted on 2006-01-01, 00:00 authored by S Mok, D Losic, Colin BarrowColin Barrow, B Turner, C Masters, L Martin, D Small
Cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease pathology. In CAA, degeneration of vascular smooth muscle cells (VSMCs) occurs close to regions of the basement membrane where the amyloid protein (Aβ) builds up. In this study, the possibility that Aβ disrupts adhesive interactions between VSMCs and the basement membrane was examined. VSMCs were cultured on a commercial basement membrane substrate (Matrigel). The presence of Aβ in the Matrigel decreased cell-substrate adhesion and cell viability. Full-length oligomeric Aβ was required for the effect, as N- and C-terminally truncated peptide analogues did not inhibit adhesion. Aβ that was fluorescently labelled at the N-terminus (fluo-Aβ) bound to Matrigel as well as to the basement membrane heparan sulfate proteoglycan (HSPG) perlecan and laminin. Adhesion of VSMCs to perlecan or laminin was decreased by Aβ. As perlecan influences VSMC viability through the extracellular signal-regulated kinase (ERK)1/2 signalling pathway, the effect of Aβ1–40 on ERK1/2 phosphorylation was examined. The level of phospho-ERK1/2 was decreased in cells following Aβ treatment. An inhibitor of ERK1/2 phosphorylation enhanced the effect of Aβ on cell adhesion. The studies suggest that Aβ can decrease VSMC viability by disrupting VSMC–extracellular matrix (ECM) adhesion.

History

Journal

Journal of neurochemistry

Volume

96

Issue

1

Pagination

53 - 64

Publisher

Raven Press (Lippincott Williams & Wilkins)

Location

[New York, N.Y.]

ISSN

0022-3042

eISSN

1471-4159

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, Lippincott Williams & Wilkins