Pei J J, Grundke-Iqbal I, Iqbal K, Bogdanovic N, Winblad B, Cowburn R F
Section for Geriatric Medicine, Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Novum, KFC, S-141 86, Huddinge, Sweden.
Brain Res. 1998 Jun 29;797(2):267-77. doi: 10.1016/s0006-8993(98)00296-0.
Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases involved in the abnormal hyperphosphorylation of tau. To have a direct effect on tau hyperphosphorylation, cdk5 protein levels and enzyme activity should be upregulated in especially those neurons that develop neurofibrillary tangles (NFTs). We studied the distribution of cdk5 immunoreactivity in neurons with or without early- and late-stage NFTs in hippocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The immunocytochemical localisation of cdk5 was compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respectively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, temporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bearing early stage NFTs. These findings suggest that this kinase might be involved in the formation of NFTs at a relatively early stage in the neocortex.
细胞周期蛋白依赖性激酶5（cdk5）是参与tau蛋白异常过度磷酸化的候选激酶之一。为了对tau蛋白过度磷酸化产生直接影响，尤其是在那些形成神经原纤维缠结（NFTs）的神经元中，cdk5蛋白水平和酶活性应该上调。我们研究了在阿尔茨海默病（AD）和对照脑的海马、内嗅、跨内嗅、颞叶和额叶皮质以及小脑中，有或没有早期和晚期NFTs的神经元中cdk5免疫反应性的分布。将cdk5的免疫细胞化学定位与分别使用针对PHF-tau（NFTs双螺旋丝中的tau，单克隆抗体AT8）和泛素的抗体获得的定位进行比较，PHF-tau和泛素分别作为早期和晚期NFTs的标志物。在海马、内嗅、跨内嗅、颞叶、额叶和小脑皮质的神经元胞体和突起中发现了cdk5和PHF-tau的免疫反应性。在缠结前神经元和带有早期NFTs的神经元中，cdk5免疫反应性明显增加。这些发现表明，这种激酶可能在新皮质相对早期阶段参与NFTs的形成。
