Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA.
Trends Cogn Sci. 2011 Nov;15(11):520-6. doi: 10.1016/j.tics.2011.09.004. Epub 2011 Oct 7.
Alzheimer's disease (AD) is the most common cause of progressive cognitive decline and dementia in adults. While the amyloid cascade hypothesis of AD posits an initiating role for the β-amyloid (Aβ) protein, there is limited understanding of why Aβ is deposited. A growing body of evidence based on in vitro, animal studies and human imaging work suggests that synaptic activity increases Aβ, which is deposited preferentially in multimodal brain regions that show continuous levels of heightened activation and plasticity across the lifespan. Imaging studies of people with genetic predispositions to AD are consistent with these findings, suggesting a mechanism whereby neural efficiency or cognitive reserve may diminish Aβ deposition. The aggregated findings unify observations from cellular and molecular studies with human cognitive neuroscience to reveal potential mechanisms of AD development.
阿尔茨海默病（AD）是导致成年人进行性认知能力下降和痴呆的最常见原因。AD 的淀粉样蛋白级联假说假定β-淀粉样蛋白（Aβ）蛋白起启动作用，但人们对 Aβ 沉积的原因知之甚少。越来越多的基于体外、动物研究和人类影像学工作的证据表明，突触活动会增加 Aβ，而 Aβ 优先沉积在多模态脑区，这些脑区在整个生命周期中持续表现出高水平的激活和可塑性。对具有 AD 遗传易感性的人的影像学研究与这些发现一致，表明一种机制，即神经效率或认知储备可能会减少 Aβ 的沉积。这些综合发现将细胞和分子研究与人类认知神经科学的观察结果统一起来，揭示了 AD 发展的潜在机制。
