Laboratory of Functional Neuroscience, Spanish Network of Excellence for Research on Neurodegenerative Diseases (CIBERNED), Pablo de Olavide University, Seville, Spain.
Sci Rep. 2017 Aug 10;7(1):7719. doi: 10.1038/s41598-017-08292-4.
Tremendous progress has been made over the last few years in understanding how sleep and amyloid-β (Aβ) cooperate to speed up the progression of Alzheimer's disease (AD). However, it remains unknown whether sleep deficits also interact with other risk factors that exacerbate the pathological cascade of AD. Based on evidence showing that higher levels of homocysteine (HCY) and sleep loss increase oxidative damage, we here investigate whether the relationship between HCY and total antioxidant capacity (TAC) is mediated by changes in objective sleep in healthy older (HO, N = 21) and mild cognitive impairment (MCI, N = 21) subjects. Results revealed that reduced TAC levels in MCI was significantly correlated with increased HCY, shorter sleep duration, lower sleep efficiency, and reduced volume of temporal regions. However, only the HCY-TAC association showed diagnostic value, and this relationship was mediated by poorer sleep quality in MCI patients. We further showed that HCY-related cerebral volume loss in MCI depended on the serial relationship between poorer sleep quality and lower TAC levels. These findings provide novel insights into how impaired sleep may contribute to maintain the relationship between HCY and oxidative stress in prodromal AD, and offer empirical foundations to design therapeutic interventions aimed to weaken this link.
在过去的几年中，人们在理解睡眠和淀粉样蛋白-β（Aβ）如何合作加速阿尔茨海默病（AD）的进展方面取得了巨大进展。然而，目前尚不清楚睡眠不足是否也与其他加重 AD 病理级联反应的风险因素相互作用。基于表明同型半胱氨酸（HCY）水平升高和睡眠不足会增加氧化损伤的证据，我们在此研究了健康老年人（HO，N=21）和轻度认知障碍（MCI，N=21）受试者的客观睡眠变化是否会介导 HCY 与总抗氧化能力（TAC）之间的关系。结果表明，MCI 中的 TAC 水平降低与 HCY 升高、睡眠时间缩短、睡眠效率降低和颞区体积减少显著相关。然而，只有 HCY-TAC 相关性具有诊断价值，并且这种相关性是由 MCI 患者的睡眠质量较差介导的。我们进一步表明，MCI 中与 HCY 相关的脑容量损失取决于睡眠质量较差与 TAC 水平降低之间的连续关系。这些发现为了解受损睡眠如何有助于维持 AD 前驱期 HCY 和氧化应激之间的关系提供了新的见解，并为设计旨在削弱这种联系的治疗干预措施提供了经验基础。
