Baum L, Masliah E, Iimoto D S, Hansen L A, Halliday W C, Saitoh T
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093.
Brain Res. 1992 Feb 21;573(1):126-32. doi: 10.1016/0006-8993(92)90121-o.
Neurofibrillary tangles (NFT) are pathological cytoskeletal structures composed of paired helical filaments (PHF), and are found in neurons of patients afflicted with many neurodegenerative disorders, including Alzheimer's disease (AD). We previously found that an antiserum against casein kinase II (CK-II) stained NFT intensely in the brain tissue of AD patients. In the current study, we found that the anti-CK-II antiserum stains NFT and neuronal inclusions in many other neurodegenerative diseases as well, including Guam-Parkinson dementia complex, chromosome 18 deletion syndrome, progressive supranuclear palsy, Kufs' disease, and Pick's disease. This antiserum reacted, in crude brain homogenates, with both a doublet of Mr 43,000 and a Mr 27,000 Da protein which could correspond to the alpha, alpha', and beta chains of CK-II. The staining of these bands was adsorbed by preincubating anti-CK-II antiserum with purified CK-II. Preincubation of brain sections with purified CK-II strongly intensified the immunostaining of NFT with anti-CK-II, suggesting that NFT may bind CK-II. In the AD brain homogenates, the particulate CK-II levels are increased whereas the cytosolic levels are decreased without a change in total CK-II levels, consistent with the idea that CK-II binds to the particulate PHF, a major constituent of NFT. In accord with these findings, purified PHF bound CK-II, but purified PHF did not contain CK-II as its component. These results suggest that CK-II might be an extraneously deposited component of NFT. Thus, the altered CK-II compartmentalization might have significant consequences in the pathogenesis of AD.
神经原纤维缠结（NFT）是由双螺旋丝（PHF）构成的病理性细胞骨架结构，在患有包括阿尔茨海默病（AD）在内的多种神经退行性疾病患者的神经元中均可发现。我们之前发现，一种针对酪蛋白激酶II（CK-II）的抗血清在AD患者脑组织中对NFT有强烈染色。在当前研究中，我们发现抗CK-II抗血清在许多其他神经退行性疾病中也能对NFT和神经元内含物进行染色，包括关岛-帕金森痴呆综合征、18号染色体缺失综合征、进行性核上性麻痹、库夫斯病和匹克病。在脑粗提物中，这种抗血清与分子量为43,000的双条带蛋白以及分子量为27,000 Da的蛋白发生反应，这两种蛋白可能分别对应CK-II的α、α'和β链。用纯化的CK-II对抗CK-II抗血清进行预孵育后，这些条带的染色被吸附。用纯化的CK-II对脑切片进行预孵育，可强烈增强抗CK-II对NFT的免疫染色，提示NFT可能结合CK-II。在AD脑匀浆中，颗粒状CK-II水平升高而胞质水平降低，总CK-II水平无变化，这与CK-II结合到NFT的主要成分颗粒状PHF上的观点一致。与这些发现相符的是，纯化的PHF能结合CK-II，但纯化的PHF并不包含CK-II作为其组成成分。这些结果表明CK-II可能是NFT的一种外源性沉积成分。因此，CK-II分布的改变可能在AD的发病机制中具有重要意义。
