NONFIBRILLAR BETA-AMYLOID PROTEIN IS ASSOCIATED WITH SMOOTH-MUSCLE CELLS OF VESSEL WALLS IN ALZHEIMER-DISEASE

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.