Alpha7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Abeta peptides and promotes cerebrovascular amyloid angiopathy.
Publication/Presentation Date
10-9-2008
Abstract
Deposition of beta-amyloid (Abeta) peptides in the walls of brain blood vessels, cerebral amyloid angiopathy (CAA), is common in patients with Alzheimer's disease (AD). Previous studies have demonstrated Abeta peptide deposition among vascular smooth muscle cells (VSMCs), but the source of the Abeta and basis for its selective deposition in VSMCs are unknown. In the present study, we examined the deposition patterns of Abeta peptides, Abeta40 and Abeta42, within the cerebrovasculature of AD and control patients using single- and double-label immunohistochemistry. Abeta40 and Abeta42 were abundant in VSMCs, especially in leptomeningeal arteries and their initial cortical branches; in later-stage AD brains this pattern extended into the microvasculature. Abeta peptide deposition was linked to loss of VSMC viability. Perivascular leak clouds of Abeta-positive material were associated primarily with arterioles. By contrast, control brains possessed far fewer Abeta42- and Abeta40-immunopositive blood vessels, with perivascular leak clouds of Abeta-immunopositive material rarely observed. We also demonstrate that VSMCs in brain blood vessels express the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), which has high binding affinity for Abeta peptides, especially Abeta42. These results suggest that the blood and blood-brain barrier permeability provide a major source of the Abeta peptides that gradually deposit in brain VSMCs, and the presence and abundance of the alpha7nAChR on VSMCs may facilitate the selective accumulation of Abeta peptides in these cells.
Volume
1234
First Page
158
Last Page
171
ISSN
0006-8993
Published In/Presented At
Clifford, P. M., Siu, G., Kosciuk, M., Levin, E. C., Venkataraman, V., D'Andrea, M. R., & Nagele, R. G. (2008). Alpha7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Abeta peptides and promotes cerebrovascular amyloid angiopathy. Brain research, 1234, 158–171. https://doi.org/10.1016/j.brainres.2008.07.092
Disciplines
Medicine and Health Sciences
PubMedID
18708033
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article