Study about Causes of Alzheimer disease

将来自患有阿尔茨海默病的家庭的4名成员和2名遗传上不相关的健康受试者的血沉棕黄层接种到仓鼠脑中。接种后18个月，大脑进行了研究，免疫染色与抗神经元，tau蛋白，泛素，和成对螺旋丝（PHF），以及通过电子显微镜。肺泡或海绵状变性最小。用2例阿尔茨海默病患者及其2名子女的血沉棕黄层接种仓鼠，其脑干下核的神经元胞体均出现抗神经丝200K蛋白抗体的强阳性染色，而对照组的血沉棕黄层接种仓鼠脑中未见此现象。电子显微镜显示胞浆内积累的10纳米神经胶质样纤维。聚集的神经丝被抗tau蛋白和抗泛素染色阳性，但不被抗PHF染色。含有大量胞浆内神经丝聚集的神经元类似于包括阿尔茨海默病在内的一些退行性疾病中的气球样神经元。结果表明，从阿尔茨海默病患者和家族成员获得的血沉棕黄层含有一种因子，该因子在下脑干核神经元中产生神经丝样纤维的胞质内积聚。

Buffy coats from 4 members of a family with Alzheimer's disease and 2 genetically unrelated healthy subjects were inoculated into the hamster brain. Eighteen months after the inoculation, the brains were studied by immunostaining with antibodies against neurofilamentts, tau, ubiquitin, and paired-helical filaments (PHF) as well as by electron microscopy. Vacuolar or spongiform degeneration was minimum. Intense positive staining by antibodies against neurofilament 200K protein was demonstrataed in neuronal perikarya of the lower brain stem nucleus in the hamster inoculated with the buffy coats from the 2 patients whith Alzheimer's disease and 2 children of the patient, which was not observed in the hamster brain inoculated with the buffy coat from the control subjects. Electron microscopy revealed intracytoplasmic accumulation of 10-nm neurofilament-like fibers. The accumulated neurofilaments were positively stained by anti-tau and anti-ubiquitin, but not by anti-PHF.The neurons containing massive intracytoplasmic neurofilament accumulation resembled ballooned neurons in some degenerative diseases including Alzheimer's disease. The results indicate that the buffy coat obtained from the patients and members of a family with Alzheimer's disease contains a factor which produces intracytoplasmic accumulation of neurofilament like fibers in neurons of the lower brain stem nuclei.