Yen S H, Gaskin F, Terry R D
Am J Pathol. 1981 Jul;104(1):77-89.
The molecular nature of neurofibrillary tangles of senile dementia of the Alzheimer type (SDAT) was studied by immunoperoxidase and immunofluorescence techniques. Five antiserums, including anti-humanbrain-2-cycle-purified-microtubule-fractions (2 x MT), anti-calf-brain-2 x MT, anti-sea-urchin-egg-tubulin, antibeef-brain-tubulin, and anti-human-brain-neurofilament(NF)-210-kilodalton(kd)-protein were tested for their binding to neurofibrillary tangles. The antihuman-2 x MT serum stained structures resembling neurofibrillary tangles, neurites of neuritic plaques, and microglialike cells in SDAT brains, but no such staining pattern was detected in normal brain sections. In neurons isolated from SDAT brains, about 40% of the tangles were labeled by the anti-human-2xMT serum with an identical pattern. Other antiserums tested did not preferentially bind tanglelike structures in tissue sections and bound to less than 5% of the tangles in isolated neurons. These results suggest that the antigenic sites of tubulin and NF proteins are not shared by neurofibrillary tangles. Different from the calf preparation, the human-2 x MT fractions contained a prominent protein band that was identical to ferritin in molecular weight and cross-reacted with anti-human-2 x MT and anti-human-ferritin serums. However, antiserums to this ferritinlike protein, or anti-ferritin, did not stain neurofibrillary tangles. Although neither the calf 2 x MT nor two other human MT fractions failed to elicit an antiserum that stained tangles, these fractions were able to remove the antihuman-2 x MT serum activity that binds to tangles. The data suggest that the protein (or proteins) that makes up neurofibrillary tangles of SDAT is present in various quantities in microtubule fractions of normal brain.
采用免疫过氧化物酶和免疫荧光技术研究了阿尔茨海默型老年性痴呆（SDAT）神经原纤维缠结的分子性质。检测了五种抗血清，包括抗人脑双循环纯化微管组分（2×MT）、抗小牛脑2×MT、抗海胆卵细胞微管蛋白、抗牛脑微管蛋白和抗人脑神经丝（NF）210千道尔顿（kd）蛋白与神经原纤维缠结的结合情况。抗人2×MT血清可使SDAT脑内类似神经原纤维缠结、神经炎性斑的神经突以及小胶质样细胞的结构着色，但在正常脑切片中未检测到这种染色模式。在从SDAT脑分离出的神经元中，约40%的缠结被抗人2×MT血清以相同模式标记。所检测的其他抗血清在组织切片中不优先结合缠结样结构，且在分离出的神经元中与不到5%的缠结结合。这些结果表明，微管蛋白和NF蛋白的抗原位点与神经原纤维缠结不共享。与小牛制品不同，人2×MT组分含有一条突出的蛋白带，其分子量与铁蛋白相同，并与抗人2×MT和抗人铁蛋白血清发生交叉反应。然而，针对这种铁蛋白样蛋白的抗血清或抗铁蛋白血清均未使神经原纤维缠结着色。尽管小牛2×MT和另外两个人MT组分均未能引发可使缠结着色的抗血清，但这些组分能够去除与缠结结合的抗人2×MT血清活性。数据表明，构成SDAT神经原纤维缠结的蛋白质在正常脑微管组分中以不同量存在。
