Granular Tau Oligomers as Intermediates of Tau Filaments

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• 作者：Sumihiro Maeda ; Naruhiko Sahara ; Yuko Saito ; Miyuki Murayama ; Yuji Yoshiike ; Hyonchol Kim ; Tomohiro Miyasaka ; Shigeo Murayama ; Atsushi Ikai ; Akihiko Takashima
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：March 27, 2007
• 年：2007
• 卷：46
• 期：12
• 页码：3856 - 3861
• 全文大小：536K
• 年卷期：v.46,no.12(March 27, 2007)
• ISSN：1520-4995

文摘

Neurofibrillary tangles (NFTs) are pathological hallmarks of several neurodegenerative disorders,including Alzheimer's disease (AD). NFTs are composed of microtubule-binding protein tau, whichassembles to form paired helical filaments (PHFs) and straight filaments. Here we show by atomic forcemicroscopy that AD brain tissue and in vitro tau form granular and fibrillar tau aggregates. CD spectralanalysis and immunostaining with conformation-dependent antibodies indicated that tau may undergoconformational changes during fibril formation. Enriched granules generated filaments, suggesting thatgranular tau aggregates may be an intermediate form of tau fibrils. The amount of granular tau aggregateswas elevated in prefrontal cortex of Braak stage I cases compared to that of Braak stage 0 cases, suggestingthat granular tau aggregation precedes PHF formation. Thus, granular tau aggregates may be a relevantmarker for the early diagnosis of tauopathy. Reducing the level of these aggregates may be a promisingtherapy for tauopathies and for promoting healthy brain aging.