Levy E, Sastre M, Kumar A, Gallo G, Piccardo P, Ghetti B, Tagliavini F
Department of Pharmacology, New York University School of Medicine, New York 10016, USA.
J Neuropathol Exp Neurol. 2001 Jan;60(1):94-104. doi: 10.1093/jnen/60.1.94.
Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid beta-protein (Abeta) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti-Abeta and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human beta amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl-terminus of Abeta(x-42) showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Abeta plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Abeta amyloid fibrils.
对阿尔茨海默病（AD）患者大脑进行的免疫组织化学分析显示，半胱氨酸蛋白酶抑制剂胱抑素C与实质和血管淀粉样沉积物中的β-淀粉样蛋白（Aβ）共定位。在所研究的任何大脑中均未观察到脑出血的迹象。免疫电子显微镜显示，淀粉样纤维与抗Aβ和抗胱抑素C抗体呈双重染色。在过度表达人β淀粉样前体蛋白的转基因小鼠大脑中的淀粉样沉积物中也观察到了胱抑素C免疫反应性。冰岛型遗传性脑出血伴淀粉样变性患者脑血管中大量变异型胱抑素C沉积被认为是导致中风的病理过程的原因。抗胱抑素C抗体强烈标记了AD患者大脑中最易发生淀粉样沉积的皮质层内的锥体神经元。用抗Aβ（x-42）羧基末端抗体进行的免疫组织化学显示，在同一神经元亚群中存在细胞内免疫反应性。胱抑素C与Aβ的关联在AD淀粉样蛋白生成中是否起主要作用，或者是该蛋白与先前形成的Aβ淀粉样纤维结合的晚期事件，仍有待确定。
