Granular tau oligomers as intermediates of tau filaments
Granular tau oligomers as intermediates of tau filaments
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DOI：
10.1021/bi061359o
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发表时间：
2007-03-27
期刊：
影响因子：
2.9
通讯作者：
Takashima, Akihiko
中科院分区：
文献类型：
--
作者：
Maeda, Sumihiro;Sahara, Naruhiko;Takashima, Akihiko
神经原纤维缠结（nft）是几种神经退行性疾病的病理标志，包括阿尔茨海默病（AD）。nft由微管结合蛋白tau组成，其组装形成成对的螺旋细丝（phf）和直细丝。在这里，我们通过原子力显微镜显示，AD脑组织和体外tau形成颗粒状和纤维状tau聚集体。CD光谱分析和构象依赖性抗体的免疫染色表明，tau可能在纤维形成过程中发生构象变化。富集颗粒生成细丝，提示颗粒状tau聚集体可能是tau原纤维的中间形式。与Braak期0例患者相比，Braak期1例患者前额皮质中颗粒状tau聚集物的数量增加，表明颗粒状tau聚集先于PHF形成。因此，颗粒状tau聚集物可能是tau病早期诊断的相关标志物。降低这些聚集物的水平可能是治疗牛头病变和促进健康大脑衰老的一种有希望的疗法。
Neurofibrillary tangles (NFTs) are pathological hallmarks of several neurodegenerative disorders, including Alzheimer's disease (AD). NFTs are composed of microtubule-binding protein tau, which assembles to form paired helical filaments (PHFs) and straight filaments. Here we show by atomic force microscopy that AD brain tissue and in vitro tau form granular and fibrillar tau aggregates. CD spectral analysis and immunostaining with conformation-dependent antibodies indicated that tau may undergo conformational changes during fibril formation. Enriched granules generated filaments, suggesting that granular tau aggregates may be an intermediate form of tau fibrils. The amount of granular tau aggregates was elevated in prefrontal cortex of Braak stage I cases compared to that of Braak stage 0 cases, suggesting that granular tau aggregation precedes PHF formation. Thus, granular tau aggregates may be a relevant marker for the early diagnosis of tauopathy. Reducing the level of these aggregates may be a promising therapy for tauopathies and for promoting healthy brain aging.