Wisniewski H M, Vorbrodt A W, Wegiel J, Morys J, Lossinsky A S
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Am J Med Genet Suppl. 1990;7:287-97. doi: 10.1002/ajmg.1320370757.
Ultrastructural, three-dimensional reconstruction of cells surrounding the amyloid star in classical plaques in Alzheimer disease (AD) and histochemical studies of the cells associated with the deposits of amyloid fibers in scrapie were carried out. These studies showed that in both diseases, the fibers appear within the smooth endoplasmic reticulum (ER) and infoldings of cytoplasmic membranes of microglia/macrophages. Additional information about the site of formation of the amyloid fibers derives from histochemical studies of the localization of nucleoside diphosphatase (NDPase) activity. In normal microglia, this enzyme is associated with smooth ER and cell membranes. In the cells that form amyloid fibers, the NDPase activity is associated with the newly formed amyloid fibers within the distended cisternae of ER and the finger-like cytoplasmic projections. In the center of the amyloid star, the NDPase activity disappears. The presence of NDPase-positive amyloid fibers in the same location, where the enzyme is found in non-amyloid-forming cells, further supports our conclusion that the microglia/macrophages are the source of amyloid deposits. These studies also show that in spite of the differences in the proteins that produce the amyloid fibers in AD and scrapie, in both diseases, the microglia/macrophages play a key role in amyloid formation.
对阿尔茨海默病（AD）经典斑块中淀粉样蛋白核心周围细胞进行了超微结构三维重建，并对羊瘙痒病中与淀粉样纤维沉积相关的细胞进行了组织化学研究。这些研究表明，在这两种疾病中，纤维均出现在小胶质细胞/巨噬细胞的光滑内质网（ER）和细胞质膜内褶中。关于淀粉样纤维形成部位的更多信息来自对核苷二磷酸酶（NDPase）活性定位的组织化学研究。在正常小胶质细胞中，这种酶与光滑内质网和细胞膜相关。在形成淀粉样纤维的细胞中，NDPase活性与内质网扩张池和指状细胞质突起内新形成的淀粉样纤维相关。在淀粉样蛋白核心中心，NDPase活性消失。在非淀粉样蛋白形成细胞中发现该酶的相同位置存在NDPase阳性淀粉样纤维，进一步支持了我们关于小胶质细胞/巨噬细胞是淀粉样蛋白沉积来源的结论。这些研究还表明，尽管AD和羊瘙痒病中产生淀粉样纤维的蛋白质存在差异，但在这两种疾病中，小胶质细胞/巨噬细胞在淀粉样蛋白形成中都起着关键作用。
