Mielke Michelle M, Haughey Norman J
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
Clin Lipidol. 2012 Oct;7(5):525-536. doi: 10.2217/clp.12.59.
Understanding the etiopathological processes of Alzheimer's disease (AD) in the preclinical and early clinical stages will be important in developing new therapeutic targets and biomarkers. There is growing consensus that nonamyloid targets will be necessary to reverse or slow AD progression. Lipidomic, metabolomic and targeted approaches have identified pathways and products of sphingolipid metabolism that are altered early in the course of AD and contribute to the neuropathological alterations associated with AD, including amyloid-β production, tau formation and neurodegeneration. In this article, we briefly review the current literature on the role of sphingolipids in the underlying pathophysiology of AD, and then discuss the current state of translating these findings to clinical populations and the potential utility of plasma sphingolipids as diagnostic and/or prognostic indicators of AD.
了解阿尔茨海默病(AD)临床前和临床早期阶段的病因病理过程对于开发新的治疗靶点和生物标志物至关重要。越来越多的人达成共识,即非淀粉样蛋白靶点对于逆转或减缓AD进展是必要的。脂质组学、代谢组学和靶向方法已经确定了鞘脂代谢的途径和产物,这些途径和产物在AD病程早期就发生改变,并导致与AD相关的神经病理改变,包括淀粉样β蛋白生成、tau蛋白形成和神经退行性变。在本文中,我们简要回顾了关于鞘脂在AD潜在病理生理学中作用的当前文献,然后讨论将这些发现转化应用于临床人群的现状以及血浆鞘脂作为AD诊断和/或预后指标的潜在效用。