老年斑
τ蛋白
神经科学
陶氏病
Tau病理学
神经突
病理
阿尔茨海默病
淀粉样蛋白(真菌学)
细胞外
发病机制
神经油
细胞内
化学
生物
神经退行性变
医学
细胞生物学
疾病
中枢神经系统
生物化学
体外
作者
Zhuohao He,Jing Guo,Jennifer D. McBride,Sneha Narasimhan,Hyesung Kim,Lakshmi Changolkar,Bin Zhang,Ronald J. Gathagan,Cuiyong Yue,Christopher G. Dengler,Anna Stieber,Magdalena Nitla,Douglas A. Coulter,Ted Abel,Kurt R. Brunden,John Q. Trojanowski,Virginia M.‐Y. Lee
出处
期刊:Nature Medicine
[Springer Nature]
日期:2017-12-04
卷期号:24 (1): 29-38
被引量:492
摘要
Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau inclusions. However, the exact mechanistic link between these two AD lesions remains enigmatic. Through injection of human AD-brain-derived pathological tau (AD-tau) into Aβ plaque-bearing mouse models that do not overexpress tau, we recapitulated the formation of three major types of AD-relevant tau pathologies: tau aggregates in dystrophic neurites surrounding Aβ plaques (NP tau), AD-like neurofibrillary tangles (NFTs) and neuropil threads (NTs). These distinct tau pathologies have different temporal onsets and functional consequences on neural activity and behavior. Notably, we found that Aβ plaques created a unique environment that facilitated the rapid amplification of proteopathic AD-tau seeds into large tau aggregates, initially appearing as NP tau, which was followed by the formation and spread of NFTs and NTs, likely through secondary seeding events. Our study provides insights into a new multistep mechanism underlying Aβ plaque-associated tau pathogenesis.
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