α7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of AP peptides and promotes cerebrovascular amyloid angiopathy

Deposition of beta-amyloid (A beta) 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 A beta peptide deposition among vascular smooth muscle cells (VSMCs), but the source of the A beta and basis for its selective deposition in VSMCs are unknown. In the present study, we examined the deposition patterns of A beta peptides, A beta 40 and A beta 42, within the cerebrovasculature of AD and control patients using single- and double-label immunohistochemistry. A beta 40 and A beta 42 were abundant in VSMCs, especially in leptomeningeal arteries and their initial cortical branches; in later-stage AD brains this pattern extended into the microvasculature. A beta peptide deposition was linked to loss of VSMC viability. Perivascular leak clouds of A beta-positive material were associated primarily with arterioles. By contrast, control brains possessed far fewer A beta 42- and A beta 40immunopositive blood vessels, with perivascular leak clouds of A beta-immunopositive material rarely observed. We also demonstrate that VSMCs in brain blood vessels express the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), which has high binding affinity for A beta peptides, especially A beta 42. These results suggest that the blood and blood-brain barrier permeability provide a major source of the A beta peptides that gradually deposit in brain VSMCs, and the presence and abundance of the alpha 7nAChR on VSMCs may facilitate the selective accumulation of A beta peptides in these cells. (C) 2008 Elsevier B.V. All rights reserved.