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 con trol brain specimens obtained from autopsies within 16 hours after dea th. 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 immuno blotting for the presence of beta PP, fragments of beta PP, and beta-p rotein. The arteries that were strongly immunopositive for beta-protei n in all layers of the walls were also positive for amyloid fibrils on thioflavine S and Congo red stainings. The focal immunostaining for b eta-protein in less affected vessels was located in the tunica media i n the cytoplasm of smooth muscle cells or formed granules between myoc ytes. The cytoplasmic beta-protein and some of the small deposits pres ent between cells were negative for amyloid fibrils. The Vessels isola ted from specimens containing beta-protein-immunoreactive material con tained 3 kD, 4.2-4.5 kD, 8.5-9 kD, and 17.5 kD beta-protein-immunoreac tive bands. These bands were not found in the samples assessed as beta -protein-negative by immunocytochemistry. These data indicate that dur ing formation of amyloid in AD vessel walls, nonfibrillar, monomeric, and oligomeric beta-protein accumulate.