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阿尔茨海默病患者血浆中特定胆碱磷脂水平的改变模拟加速衰老。

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

机构信息

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

Peroxisomal Diseases Laboratory, The Hugo W Moser Research Institute, The Kennedy Krieger Institute, Baltimore, MD, USA.

出版信息

J Alzheimers Dis. 2018;62(2):841-854. doi: 10.3233/JAD-171036.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VITA) study, a longitudinal, population-based birth cohort study, at baseline and after 90 months or at diagnosis of probable AD. We determined the levels of specific choline phospholipids, some of which have been suggested as potential biomarkers for the prediction of AD. Our results show that during normal aging the levels of lysophosphatidylcholine, choline plasmalogen, and lyso-platelet activating factor increase significantly. Notably, we observed similar but more pronounced changes in the group that developed probable AD. Thus, our results imply that, in terms of choline-containing plasma phospholipids, the conversion to AD mimics an accelerated aging process. We conclude that age, even in the comparatively short time frame between 75 and 82.5 years, is a crucial factor in the quest for plasma lipid biomarkers for AD that must be carefully considered in future studies and trials.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,且其发病率呈持续上升趋势。目前,鉴定出易于测量的生物标志物,以辅助 AD 的预测和早期诊断,是主要的研究目标。在这方面,人类患者外周血中的脂质代谢物最近受到了极大关注。在这里,我们分析了维也纳多瑙河老龄化研究(VITA)中 174 名参与者(基线时无痴呆;平均年龄:75.70±0.44 岁)的血浆,该研究是一项纵向、基于人群的出生队列研究,分别在基线时、90 个月时或确诊可能的 AD 时进行了检测。我们测定了特定胆碱磷脂的水平,其中一些被认为是预测 AD 的潜在生物标志物。我们的研究结果表明,在正常衰老过程中,溶血磷脂酰胆碱、胆碱脑苷脂和溶血小板激活因子的水平显著增加。值得注意的是,我们在发展为可能的 AD 的组中观察到了类似但更明显的变化。因此,我们的研究结果表明,就含有胆碱的血浆磷脂而言,向 AD 的转变模拟了加速衰老过程。我们得出的结论是,年龄是 AD 血浆脂质生物标志物研究的关键因素,即使在 75 岁至 82.5 岁之间相对较短的时间框架内也是如此,在未来的研究和试验中必须对此加以仔细考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49fe/5842786/6de0f0d72535/jad-62-jad171036-g001.jpg

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