Non-fibrillar beta-amyloid protein is associated with smooth muscle cells of vessel walls in Alzheimer disease

Abstract

Meningeal blood vessels were studied in Alzheimer disease (AD) and control brain specimens obtained from autopsies within 16 hours after death. Serial sections were stained with thioflavine S and Congo red and immunostained for the presence of beta-amyloid precursor protein (beta PP) and beta-protein and for smooth muscle-specific proteins myosin, alpha-actin, and desmin. Isolated blood vessels were studied by immunoblotting for the presence of beta PP, fragments of beta PP, and beta-protein. The arteries that were strongly immunopositive for beta-protein in all layers of the walls were also positive for amyloid fibrils on thioflavine S and Congo red stainings. The focal immunostaining for beta-protein in less affected vessels was located in the tunica media in the cytoplasm of smooth muscle cells or formed granules between myocytes. The cytoplasmic beta-protein and some of the small deposits present between cells were negative for amyloid fibrils. The vessels isolated from specimens containing beta-protein-immunoreactive material contained 3 kD, 4.2-4.5 kD, 8.5-9 kD, and 17.5 kD beta-protein-immunoreactive bands. These bands were not found in the samples assessed as beta-protein-negative by immunocytochemistry. These data indicate that during formation of amyloid in AD vessel walls, nonfibrillar, monomeric, and oligomeric beta-protein accumulate.