Neuroscience Discovery, Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland.
Karuna Therapeutics, Inc., Boston, MA, United States.
Neurosci Lett. 2019 Sep 14;709:134366. doi: 10.1016/j.neulet.2019.134366. Epub 2019 Jul 20.
The ε4 allele of the apolipoprotein E gene represents the most widely reproduced and robust susceptibility loci for the most common late onset and sporadic forms of Alzheimer's disease. While the discovery of this now widely replicated association was reported more than 25 years ago, few therapeutic interventions that specifically target the apolipoprotein pathway in brain have emerged. Here we discuss our current understanding of apolipoprotein E biology in brain, its relationship to the pathogenesis of Alzheimer's disease and present potential future avenues for exploration that may be amenable to drug development.
载脂蛋白 E 基因的 ε4 等位基因是最广泛复制和稳健的易感性基因，与最常见的迟发性和散发性阿尔茨海默病形式有关。虽然这一现已广泛复制的关联的发现已有 25 多年的历史，但针对大脑中载脂蛋白途径的治疗干预措施却很少。在这里，我们讨论了我们目前对大脑中载脂蛋白 E 生物学的理解，以及它与阿尔茨海默病发病机制的关系，并提出了一些可能适合药物开发的潜在未来探索途径。
