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对20种血浆代谢物进行胆汁酸定量分析,结果表明石胆酸是阿尔茨海默病的一种潜在生物标志物。

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer's disease.

作者信息

Marksteiner Josef, Blasko Imrich, Kemmler Georg, Koal Therese, Humpel Christian

机构信息

Department of Psychiatry and Psychotherapy A, General Hospital, Hall, Austria.

Laboratory of Psychiatry and Experimental Alzheimer's Research, Medical University of Innsbruck, Innsbruck, Austria.

出版信息

Metabolomics. 2018;14(1):1. doi: 10.1007/s11306-017-1297-5. Epub 2017 Nov 17.

Abstract

INTRODUCTION

There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer's disease (AD) and monitor disease progression. Liquid chromatography-mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

OBJECTIVES

The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

METHODS

Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

RESULTS

Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50 ± 6 nM, p = 0.004) compared to healthy controls (32 ± 3 nM). Lithocholic acid plasma levels of MCI patients (41 ± 4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p < 0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8-9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

CONCLUSION

In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.

摘要

引言

目前仍迫切需要一种广泛可用、价格低廉且可靠的方法来诊断阿尔茨海默病(AD)并监测疾病进展。液相色谱 - 质谱联用(LC - MS)是一种强大的分析技术,具有非常高的灵敏度和特异性。

目的

本研究的目的是使用基于LC - MS技术的Biocrates生命科学公司的新型试剂盒测量20种胆汁酸的浓度。

方法

对30名认知健康受试者、20名轻度认知障碍(MCI)患者和30名AD患者的血浆中的20种胆汁酸代谢物进行定量测量。

结果

与健康对照(32±3 nM)相比,AD患者血浆中石胆酸水平显著升高(50±6 nM,p = 0.004)。MCI患者的石胆酸血浆水平(41±4 nM)与健康受试者或AD患者无显著差异。与MCI患者相比,AD患者的甘氨鹅脱氧胆酸、甘氨脱氧胆酸和甘氨石胆酸水平显著更高(p < 0.05)。健康受试者、MCI患者和AD患者之间所有其他胆酸代谢物无显著差异。ROC分析显示总体准确率约为66%。使用判别分析对患者进行分类,我们发现23例中有15例被正确诊断。我们进一步表明,在8 - 9年的随访期内,健康受试者转变为AD患者时,LCA水平增加约3.2倍。通路分析将这些变化与推测的有毒胆固醇通路联系起来。

结论

总之,尽管诊断准确性存在局限性,但4种胆汁酸可能有助于诊断血浆样本中的AD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c46a/5725507/f857d60d2246/11306_2017_1297_Fig1_HTML.jpg

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