Clavaguera F, Hench J, Goedert M, Tolnay M
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Neuropathol Appl Neurobiol. 2015 Feb;41(1):47-58. doi: 10.1111/nan.12197.
Filaments made of hyperphosphorylated tau protein are encountered in a number of neurodegenerative diseases referred to as 'tauopathies'. In the most prevalent tauopathy, Alzheimer's disease, tau pathology progresses in a stereotypical manner with the first lesions appearing in the locus coeruleus and the entorhinal cortex from where they appear to spread to the hippocampus and neocortex. Propagation of tau pathology is also characteristic of argyrophilic grain disease, where the tau lesions appear to spread throughout distinct regions of the limbic system. These findings strongly implicate neurone-to-neurone propagation of tau aggregates. Isoform composition and morphology of tau filaments can differ between tauopathies suggesting the existence of conformationally diverse tau strains. Altogether, this points to prion-like mechanisms in the pathogenesis of tauopathies.
由高度磷酸化的tau蛋白构成的细丝出现在许多被称为“tau蛋白病”的神经退行性疾病中。在最常见的tau蛋白病——阿尔茨海默病中，tau病理变化以一种刻板的方式进展，最初的病变出现在蓝斑和内嗅皮质，随后似乎从这些部位扩散到海马体和新皮质。tau病理变化的传播也是嗜银颗粒病的特征，在这种疾病中，tau病变似乎扩散到边缘系统的不同区域。这些发现强烈暗示了tau聚集体在神经元之间的传播。tau细丝的异构体组成和形态在不同的tau蛋白病中可能有所不同，这表明存在构象多样的tau毒株。总之，这表明tau蛋白病的发病机制中存在类朊病毒机制。
