Grundke-Iqbal I, Johnson A B, Terry R D, Wisniewski H M, Iqbal K
Ann Neurol. 1979 Dec;6(6):532-7. doi: 10.1002/ana.410060612.
A 50,000-dalton polypeptide has been purified from fractions enriched with neurofibrillary tangles of paired helical filaments from human autopsy specimens of Alzheimer disease and senile dementia of the Alzheimer type. An antiserum to this polypeptide was raised in a rabbit. This antiserum formed an immunoprecipitation line with the purified antigen and with human neurotubules in ouchterlony double-diffusion plates. The reactivity of the anti-paired helical filament protein serum with neurofibrillary tangles was studied by immunofluorescence on cryostat sections of hippocampus from Alzheimer autopsy tissue and by the peroxidase-antiperoxidase technique on paraffin sections of an Alzheimer brain biopsy. The tangles were stained with the antiserum in both systems. Preimmune rabbit serum and unrelated hyperimmune sera, used as controls, did not stain the tangles. These results show that the 50,000-dalton polypeptide purified from the neurofibrillary tangle-enriched fractions is a constituent of Alzheimer neurofibrillary tangles and, perhaps, of the paired helical filaments of which the tangles are composed.
从阿尔茨海默病和阿尔茨海默型老年痴呆症患者尸检标本中富含神经原纤维缠结的双螺旋丝组分中纯化出一种50000道尔顿的多肽。用该多肽免疫家兔制备了抗血清。在欧氏双扩散平板中,该抗血清与纯化抗原及人神经微管形成免疫沉淀线。采用免疫荧光法对阿尔茨海默病尸检组织海马的低温切片进行研究,并采用过氧化物酶-抗过氧化物酶技术对阿尔茨海默病脑活检的石蜡切片进行研究,以探讨抗双螺旋丝蛋白血清与神经原纤维缠结的反应性。在这两种检测系统中,抗血清均能使缠结染色。作为对照的免疫前兔血清和无关的超免疫血清均未使缠结染色。这些结果表明,从富含神经原纤维缠结的组分中纯化出的50000道尔顿多肽是阿尔茨海默病神经原纤维缠结的一个组成成分,或许也是构成缠结的双螺旋丝的组成成分。