Helen and Robert Appel Alzheimer's Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, USA.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, USA.
Neurosci Lett. 2019 Jul 13;705:183-194. doi: 10.1016/j.neulet.2019.04.022. Epub 2019 Apr 25.
Alzheimer's disease (AD) is characterized by two major pathological lesions in the brain, amyloid plaques and neurofibrillary tangles (NFTs) composed mainly of amyloid-β (Aβ) peptides and hyperphosphorylated tau, respectively. Although accumulation of toxic Aβ species in the brain has been proposed as one of the important early events in AD, continued lack of success of clinical trials based on Aβ-targeting drugs has triggered the field to seek out alternative disease mechanisms and related therapeutic strategies. One of the new approaches is to uncover novel roles of pathological tau during disease progression. This review will primarily focus on recent advances in understanding the contributions of tau to AD.
阿尔茨海默病(AD)的特征是大脑中有两种主要的病理病变,即由淀粉样β(Aβ)肽和过度磷酸化的 tau 分别组成的淀粉样斑块和神经原纤维缠结(NFTs)。尽管脑内有毒性 Aβ 物质的积累被认为是 AD 的重要早期事件之一,但基于 Aβ 靶向药物的临床试验的持续失败促使该领域寻求替代疾病机制和相关治疗策略。一种新方法是揭示病理 tau 在疾病进展过程中的新作用。本综述将主要关注对 tau 在 AD 中的作用的最新理解进展。