Tagliavini F, Ghiso J, Timmers W F, Giaccone G, Bugiani O, Frangione B
Department of Pathology, New York University Medical Center, New York.
Lab Invest. 1990 Jun;62(6):761-7.
Polyclonal antibodies to synthetic peptides homologous to amino acid residues 45-62, 597-624, and 676-695 of the predicted sequence of Alzheimer's amyloid precursor protein (APP) were used to investigate the site of origin of APP, and the relationship between APP and amyloid protein in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). Cortical sections as well as homogenates of isolated leptomeningeal and cortical microvessels from three patients with AD, two patients with HCHWA-D, and two nondemented controls were probed. In vessel extracts of both groups of patients and the controls, APP was detected as a set of proteins with electrophoretic mobility of 105 to 135 kilodaltons. In cortical sections of all subjects, APP immunoreactivity was found in leptomeningeal and cortical vessel walls. In patients with AD and HCHWA-D, APP and amyloid fibrils coexisted in the same vessels. Moreover, APP immunoreactivity was found in association with 50% of senile plaques in AD brains, but was not evidenced in parenchymal amyloid deposits in patients with HCHWA-D. These data suggest that the vascular system is a source of APP and that the processing of APP into insoluble fibrils in AD and HCHWA-D may take place in situ.
针对与阿尔茨海默病淀粉样前体蛋白（APP）预测序列中氨基酸残基45 - 62、597 - 624和676 - 695同源的合成肽的多克隆抗体，被用于研究APP的起源部位，以及APP与阿尔茨海默病（AD）和荷兰型遗传性脑出血伴淀粉样变性（HCHWA - D）中淀粉样蛋白之间的关系。对来自3例AD患者、2例HCHWA - D患者和2例非痴呆对照的皮质切片以及分离的软脑膜和皮质微血管匀浆进行检测。在两组患者和对照的血管提取物中，APP被检测为一组电泳迁移率为105至135千道尔顿的蛋白质。在所有受试者的皮质切片中，APP免疫反应性在软脑膜和皮质血管壁中被发现。在AD和HCHWA - D患者中，APP和淀粉样纤维共存于同一血管中。此外，在AD脑50%的老年斑中发现APP免疫反应性，但在HCHWA - D患者的实质淀粉样沉积物中未得到证实。这些数据表明，血管系统是APP的一个来源，并且在AD和HCHWA - D中APP加工成不溶性纤维可能在原位发生。
