Wisniewski H M, Wegiel J
Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Acta Neuropathol. 1994;87(3):233-41. doi: 10.1007/BF00296738.
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.
对三名阿尔茨海默病（AD）患者软脑膜血管的超微结构研究表明，动脉和小动脉中膜的β-淀粉样蛋白沉积物是由平滑肌细胞产生的。似乎肌肉细胞肌膜囊泡分泌的可溶性β蛋白在基膜中聚合成淀粉样纤维。被困在淀粉样沉积物中的心肌细胞会退化并死亡。平滑肌细胞最常见和最严重的退化出现在血管中膜的外层和中层。在淀粉样变性变化的更晚期阶段，中膜的内层也会受累。发生严重变化的血管中膜由淀粉样沉积物和细胞碎片组成。死亡心肌细胞周围的淀粉样纤维也会发生降解。它们失去纤维状外观，变成絮状、颗粒状、无定形的蛋白质物质；然而，这种物质在β-淀粉样蛋白免疫染色中持续呈阳性。这项研究表明，平滑肌细胞形成淀粉样蛋白涉及一条分泌途径。我们的数据表明，平滑肌细胞分泌非纤维状β蛋白或含β蛋白的肽，并且非纤维状β蛋白向纤维状β-淀粉样蛋白的转化发生在基底膜环境中。
