Department of Anatomy, Loma Linda University School of Medicine, Evans Hall B08, 24785 Stewart Street, Loma Linda, CA 92354, United States.
Ageing Res Rev. 2014 Jan;13:10-2. doi: 10.1016/j.arr.2013.10.001. Epub 2013 Nov 16.
The amyloid cascade hypothesis, which implicates the amyloid Aβ peptide as the pathological initiator of both familial and sporadic, late onset Alzheimer's disease (AD), continues to guide the majority of research. We believe that current evidence does not support the amyloid cascade hypothesis for late onset AD. Instead, we propose that Aβ is a key regulator of brain homeostasis. During AD, while Aβ accumulation may occur in the long term in parallel with disease progression, it does not contribute to primary pathogenesis. This view predicts that amyloid-centric therapies will continue to fail, and that progress in developing successful alternative therapies for AD will be slow until closer attention is paid to understanding the physiological function of Aβ and its precursor protein.
淀粉样蛋白级联假说，将淀粉样蛋白 Aβ 肽作为家族性和散发性、晚发性阿尔茨海默病（AD）的病理起始因素，该假说继续指导着大多数研究。我们认为，目前的证据并不支持淀粉样蛋白级联假说用于解释晚发性 AD。相反，我们提出 Aβ 是大脑内稳态的关键调节剂。在 AD 中，虽然 Aβ 积累可能会在疾病进展的同时在长期内发生，但它不会导致主要的发病机制。这种观点预测，以淀粉样蛋白为中心的治疗方法将继续失败，并且在开发 AD 成功的替代疗法方面进展缓慢，除非更加关注理解 Aβ及其前体蛋白的生理功能。
