Inoue S, Kisilevsky R
Department of Anatomy and Cell Biology, McGill Univeristy, Montreal, Quebec, Canada.
Ital J Anat Embryol. 2001;106(2 Suppl 1):93-102.
Beta amyloid fibrils were examined in situ in the cerebral cortex of brains from patients with Alzheimer's disease using high resolution ultrastructural and immunohistochemical techniques. The main body of the fibril was identical with that of microfibrils and was made up of a core containing amyloid P component (AP), and a surface layer. Beta amyloid protein (Abeta) in the form of 1 nm wide flexible filaments was associated with the external surface of the microfibril. In cerebrovascular amyloid angiopathy the fibrils were formed at the outer surface of the vascular basement membrane. Overproduction of microfibrils has been reported at the basement membrane of "leaky" capillaries including the glomerular capillary in disease or leaky alveolar-capillary walls of normal lungs. Similarly, in Alzheimer's disease overproduction of microfibril-like beta amyloid fibrils in amyloid angiopathy coincided with breakdown of the blood-brain barrier of the cerebromicrovasculature. Thus, in the above three locations, the presence of abundant microfibrils, or microfibril-like structures, may be related to plasma which leaks out of the circulation into the adjoining vascular basement membrane. AP is an essential constituent of microfibrils and since the only site where AP is available in the cerebral cortex is in leaky microvasculature, a chronic, steady supply of AP into perivascular areas may be the cause of overproduction of microfibrils. Brain "microfibrils" may further be altered pathologically into beta amyloid fibrils by the addition of Abeta. The origin of the fibrils in senile plaques may also be the microvasculature since in the area of the plaques no source of AP is apparent.
利用高分辨率超微结构和免疫组织化学技术，对阿尔茨海默病患者大脑皮质中的β淀粉样纤维进行了原位检测。纤维的主体与微纤维相同，由含有淀粉样P成分（AP）的核心和表层组成。呈1纳米宽柔性细丝形式的β淀粉样蛋白（Abeta）与微纤维的外表面相关联。在脑血管淀粉样血管病中，纤维在血管基底膜的外表面形成。据报道，在包括疾病中的肾小球毛细血管或正常肺脏的渗漏性肺泡 - 毛细血管壁在内的“渗漏”毛细血管的基底膜处，微纤维产生过多。同样，在阿尔茨海默病中，淀粉样血管病中微纤维样β淀粉样纤维的产生过多与脑微血管系统血脑屏障的破坏同时发生。因此，在上述三个部位，大量微纤维或微纤维样结构的存在可能与从循环中渗漏到相邻血管基底膜的血浆有关。AP是微纤维的重要组成部分，由于大脑皮质中AP唯一可获得的部位是渗漏的微血管，因此向血管周围区域持续稳定供应AP可能是微纤维产生过多的原因。脑“微纤维”可能通过添加Abeta在病理上进一步改变为β淀粉样纤维。老年斑中纤维的起源也可能是微血管，因为在斑块区域没有明显的AP来源。
