Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore.
Bioessays. 2017 Sep;39(9). doi: 10.1002/bies.201700062. Epub 2017 Jul 21.
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti-amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β-protein and its precursor, the amyloid precursor protein (APP) are but a part of the disease cascade. Further, risk of AD can be modulated by a number of factors, the most impactful being the ɛ4 isoform of apolipoprotein E (apoE). A recent study reported a novel isoform-dependent transcriptional regulation of APP by apoE. These interesting new results add to the myriad of mechanisms that have been proposed to explain how apoE4 enhances AD risk, highlighting the complexities of not only apoE and AD pathophysiology, but also of disease itself. Also see the video abstract here: https://youtu.be/yd14MBdPkCY.
阿尔茨海默病（AD）是最常见的痴呆症形式，它会逐渐破坏大脑网络，损害记忆、语言和认知能力。虽然淀粉样蛋白假说仍然是解释 AD 病理生理学的主要提出机制，但抗淀粉样蛋白治疗策略尚未转化为有用的疗法，这表明淀粉样蛋白 β 蛋白及其前体淀粉样前体蛋白（APP）只是疾病级联反应的一部分。此外，AD 的风险可以通过多种因素来调节，最具影响力的是载脂蛋白 E（apoE）的ɛ4 同工型。最近的一项研究报告了 apoE 对 APP 的新型同工型依赖性转录调控。这些有趣的新结果增加了许多已经提出的解释 apoE4 如何增加 AD 风险的机制，不仅强调了 apoE 和 AD 病理生理学的复杂性，也强调了疾病本身的复杂性。也可以在此处观看视频摘要：https://youtu.be/yd14MBdPkCY。
