Beta-amyloid formation by myocytes of leptomeningeal vessels.

Ultrastructural study of the leptomeningeal vessels of three subjects with Alzheimer's disease (AD) shows that beta-amyloid deposits in the media of arteries and arterioles are produced by smooth muscle cells. It appears that the soluble beta-protein secreted by sarcolemmal vesicles of the muscle cell polymerizes into amyloid fibrils in basal lamina. Myocytes trapped in amyloid deposits degenerate and die. The most common and severe degeneration of smooth muscle cells is seen in the external and medial zone of the vascular media. In more advanced stages of amyloidotic changes, the internal zone of media is also involved. The media of vessels with severe changes consists of amyloid deposits and cell debris. Amyloid fibrils around the dead myocytes also undergo degradation. They lose their fibrillar appearance and become floccular, granular, amorphous proteinous material; however, this material is continually positive in immunostaining for beta-amyloid. This study suggests that amyloid formation by smooth muscle cells involves a secretory path. Our data indicate that the smooth muscle cell secretes nonfibrillar beta-protein or beta-protein containing peptides and that conversion of nonfibrillar into fibrillar beta-amyloid takes place in the environment of the basement membrane.