Vascular β-amyloid in Alzheimer's disease angiopathy is produced by proliferating and degenerating smooth muscle cells

Abstract

Meningeal and cerebral blood vessels were studied in Alzheimer's disease (AD), Down's syndrome (DS), and control brain specimens. Serial sections were double-and triple-immunostained for β-protein, smooth muscle cells, and leukocytes or macrophages/monocytes. At early stages of amyloidogenesis, β-protein immunoreactive material is present in vascular tunica media in the cytoplasm of myocytes or extracellularly between smooth muscle cells. The sites of β-protein deposition exhibit increased immunoreactivity for C-terminal βPP, but not for N-terminal βPP. The cells around small β-protein deposits express actin, myosin, and vimentin but most lack another smooth muscle-specific protein—desmin. These muscle cells often have swollen nuclei and express the proliferating cell nuclear antigen. At more advanced stages of amyloidosis, the tunica media is replaced by amyloid deposits with only scanty smooth muscle cells. Macrophages and leukocytes are not present at the sites of amyloid formation. The results indicate that the cells engaged information of vascular amyloid are proliferating and degenerating smooth muscle cells of the tunica media.