Granular tau oligomers as intermediates of tau filaments

Sumihiro Maeda, Naruhiko Sahara, Yuko Saito, Miyuki Murayama, Yuji Yoshiike, Hyonchol Kim, Tomohiro Miyasaka, Shigeo Murayama, Atsushi Ikai, Akihiko Takashima

研究成果: Article査読

218 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3856-3861
ページ数6
ジャーナルBiochemistry
46
12
DOI
出版ステータスPublished - 2007 3月 27
外部発表はい

ASJC Scopus subject areas

  • 生化学

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