Brunden Kurt R, Trojanowski John Q, Lee Virginia M-Y
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Alzheimers Dis. 2008 Aug;14(4):393-9. doi: 10.3233/jad-2008-14406.
The discovery that mutations within the tau gene lead to frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) provided direct evidence that tau alterations can lead to neurodegenerative disease. While the presence of tau fibrils and tangles is a common feature of all tauopathies, including Alzheimer's disease (AD), data are emerging from biochemical, cell-based and transgenic mouse studies which suggest that a pre-fibrillar form of pathological tau may play a key role in eliciting central nervous system neurodegeneration and behavioral impairments. Herein we review recent findings that implicate diffusible tau pathology in the onset of neurodegeneration, and discuss the implications of these findings as they relate to tau tangles and possible therapeutic strategies for the treatment of AD and related tauopathies.
tau基因内的突变会导致与17号染色体相关的额颞叶痴呆伴帕金森综合征（FTDP - 17），这一发现提供了直接证据，表明tau改变可导致神经退行性疾病。虽然tau原纤维和缠结的存在是所有tau蛋白病（包括阿尔茨海默病（AD））的共同特征，但来自生化、细胞和转基因小鼠研究的数据表明，病理性tau的前纤维形式可能在引发中枢神经系统神经退行性变和行为障碍中起关键作用。在此，我们综述了近期将可扩散的tau病理学与神经退行性变的发病联系起来的研究发现，并讨论了这些发现与tau缠结的关系以及治疗AD和相关tau蛋白病的可能治疗策略。
