Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Carbondale, IL 62794, USA.
J Alzheimers Dis. 2010;22(2):393-9. doi: 10.3233/JAD-2010-100846.
The amyloid cascade hypothesis has guided much of the research into Alzheimer's disease (AD) over the last 25 years. We argue that the hypothesis of amyloid-β (Aβ) as the primary cause of dementia may not be fully correct. Rather, we propose that decline in brain metabolic activity, which is tightly linked to synaptic activity, actually underlies both the cognitive decline in AD and the deposition of Aβ. Aβ may further exacerbate metabolic decline and result in a downward spiral of cognitive function, leading to dementia. This novel interpretation can tie the disparate risk factors for dementia to a unifying hypothesis and present a roadmap for interventions to decrease the prevalence of dementia in the elderly population.
淀粉样蛋白级联假说指导了过去 25 年来对阿尔茨海默病（AD）的大部分研究。我们认为，淀粉样蛋白-β（Aβ）作为痴呆主要原因的假说可能并不完全正确。相反，我们提出，与突触活动密切相关的大脑代谢活性的下降实际上是 AD 认知能力下降和 Aβ沉积的基础。Aβ 可能进一步加剧代谢下降，导致认知功能的螺旋式下降，从而导致痴呆。这种新的解释可以将痴呆的不同风险因素与一个统一的假说联系起来，并为干预措施提供路线图，以降低老年人群中痴呆的患病率。
