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Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease
Journal of Pharmaceutical Analysis ( IF 6.1 ) Pub Date : 2021-07-14 , DOI: 10.1016/j.jpha.2021.07.005
Jericha Mill 1 , Vihar Patel 2 , Ozioma Okonkwo 3 , Lingjun Li 1, 4 , Thomas Raife 2
Affiliation  

Diagnosing Alzheimer's disease (AD) in the early stage is challenging. Informative biomarkers can be of great value for population-based screening. Metabolomics studies have been used to find potential biomarkers, but commonly used tissue sources can be difficult to obtain. The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD. Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue, erythrocytes are plentiful and easily accessed. Moreover, erythrocytes are metabolically active, a feature that distinguishes this sample source from other bodily fluids like plasma and urine. In this preliminary pilot study, the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD (control (CTRL)) were compared. Whole blood was collected post-mortem and erythrocytes were analyzed using ultra-performance liquid chromatography tandem mass spectrometry. Over 750 metabolites were identified in AD and CTRL erythrocytes. Seven were increased in AD while 24 were decreased (P<0.05). The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism. Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients. Sphingolipids have been previously implicated in AD and other neurological conditions. Furthermore, previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal, healthy adults. Together, these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.



中文翻译:

红细胞鞘脂类作为阿尔茨海默病的生物标志物

早期诊断阿尔茨海默病 (AD) 具有挑战性。信息丰富的生物标志物对于基于人群的筛查具有重要价值。代谢组学研究已被用于寻找潜在的生物标志物,但常用的组织来源可能很难获得。本研究的目的是确定红细胞代谢物谱在 AD 筛查中的潜在效用。与脑脊液和脑组织等一些常用来源不同,红细胞数量丰富且易于获取。此外,红细胞具有新陈代谢活性,这一特征可将此样本来源与血浆和尿液等其他体液区分开来。在这项初步初步研究中,比较了 10 名经组织病理学证实的 AD 患者和 10 名无 AD 患者(对照 (CTRL))的红细胞代谢组。死后收集全血,并使用超高效液相色谱串联质谱法分析红细胞。在 AD 和 CTRL 红细胞中鉴定出超过 750 种代谢物。AD 增加了 7 个,减少了 24 个(P <0.05)。大多数在 AD 中增加的代谢物与氨基酸代谢有关,而所有减少的代谢物都与脂质代谢有关。潜在生物标志物中最突出的是 10 种鞘脂或鞘脂相关物质,它们在 AD 患者中持续减少。鞘脂以前曾与 AD 和其他神经系统疾病有关。此外,先前的研究表明,红细胞鞘脂浓度在正常、健康的成年人中差异很大。总之,这些观察表明某些红细胞脂质表型可能是 AD 发展风险的标志。

更新日期:2021-07-14
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