Maeda Sumihiro, Sahara Naruhiko, Saito Yuko, Murayama Shigeo, Ikai Atsushi, Takashima Akihiko
Lab for Alzheimer's Disease, Brain Science Institute, RIKEN, 2-1 Hirosaswa, Wako, Saitama 351-0198, Japan.
Neurosci Res. 2006 Mar;54(3):197-201. doi: 10.1016/j.neures.2005.11.009. Epub 2006 Jan 6.
Development of neurofibrillary tangles (NFTs) is a pathological hallmark in various neurodegenerative disorders including Alzheimer's disease (AD). Recently, we identified a granular tau oligomer having a pre-filamentous structure. To determine the role of this oligomer in NFT formation, we quantified the amount of granular tau oligomer in 21 frontal cortex samples, each displaying varying degrees of Braak-staged NFT pathology. Here we report that granular tau oligomer levels in frontal cortex were significantly increased, even in brains displaying Braak-stage I neuropathology, a stage at which clinical symptoms of AD and NFTs in frontal cortex are believed to be absent. This suggests that increases in granular tau oligomer levels occur before NFTs form and before individuals manifest clinical symptoms of AD. Increased granular tau oligomer levels, therefore, may lead to NFT formation in frontal cortex, eventually leading to the development of AD. Thus, increases in granular tau oligomer levels may represent a very early sign of NFT formation and AD.
神经原纤维缠结（NFTs）的形成是包括阿尔茨海默病（AD）在内的各种神经退行性疾病的病理标志。最近，我们鉴定出一种具有丝状前结构的颗粒状tau寡聚体。为了确定这种寡聚体在NFT形成中的作用，我们对21个额叶皮质样本中的颗粒状tau寡聚体数量进行了定量，每个样本都表现出不同程度的Braak分期NFT病理。在此我们报告，即使在显示Braak I期神经病理学的大脑中，额叶皮质中的颗粒状tau寡聚体水平也显著增加，据信该阶段AD的临床症状和额叶皮质中的NFT不存在。这表明颗粒状tau寡聚体水平的增加发生在NFT形成之前以及个体出现AD临床症状之前。因此，颗粒状tau寡聚体水平的增加可能导致额叶皮质中NFT的形成，最终导致AD的发展。因此，颗粒状tau寡聚体水平的增加可能代表NFT形成和AD的非常早期迹象。
