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

Research output: Contribution to journalArticlepeer-review

182 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3856-3861
Number of pages6
JournalBiochemistry
Volume46
Issue number12
DOIs
Publication statusPublished - 2007 Mar 27
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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