Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; email:
Annu Rev Pathol. 2024 Jan 24;19:345-370. doi: 10.1146/annurev-pathmechdis-051222-120750. Epub 2023 Oct 13.
Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein forms pathologic fibrillar aggregates that are typically closely associated with neuronal cell death, leading to varied clinical phenotypes including dementia, movement disorders, and motor neuron disease. In this review, we describe the clinicopathologic features of tauopathies and highlight recent advances in understanding the mechanisms that lead to spread of pathologic aggregates through interconnected neuronal pathways. The cell-to-cell propagation of tauopathy is then linked to posttranslational modifications, tau fibril structural variants, and the breakdown of cellular protein quality control.
tau 病是一组异质性的、进行性的和致命的神经退行性疾病,其特征是中枢神经系统中异常的 tau 包含物。tau 蛋白形成病理性纤维状聚集物,通常与神经元细胞死亡密切相关,导致不同的临床表型,包括痴呆、运动障碍和运动神经元病。在这篇综述中,我们描述了 tau 病的临床病理特征,并强调了理解导致病理性聚集物通过相互连接的神经元途径传播的机制的最新进展。tau 病的细胞间传播与翻译后修饰、tau 纤维结构变体和细胞蛋白质质量控制的破坏有关。