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一种用于鉴定阿尔茨海默病患者血液中生物标志物的代谢组学方法。

A metabolomic approach to identifying biomarkers in blood of Alzheimer's disease.

机构信息

Department of Laboratory Medicine Chang Gung Memorial Hospital Taoyuan Taiwan.

Department of Medical Biotechnology and Laboratory Science College of Medicine Chang Gung University Taoyuan Taiwan.

出版信息

Ann Clin Transl Neurol. 2019 Feb 27;6(3):537-545. doi: 10.1002/acn3.726. eCollection 2019 Mar.

Abstract

OBJECTIVE

This study aims to identify metabolites with altered levels of expression in patients with early and progressive stages of Alzheimer's disease (AD).

METHODS

All participants of the study underwent genetic screening and were diagnosed using both neuropsychological assessment and amyloid imaging before metabolome analysis. According to these assessments, the patients were classified as normal ( = 15), with mild cognitive impairment ( = 10), and with AD ( = 15).

RESULTS

Using a targeted metabolomic approach, we found that plasma levels of C3, C5, and C5-DC acylcarnitines, arginine, phenylalanine, creatinine, symmetric dimethylarginine (SDMA) and phosphatidylcholine ae C38:2 were significantly altered in patients with early and progressive stages of AD. We created a predictive model based on the decision tree that included three main parameters: age, arginine and C5 plasma concentrations. The model distinguished AD patients from other participants with 60% sensitivity and 86.7% specificity. For healthy controls, the sensitivity was 85.7% and specificity was 61.5%. Multivariate ROC analysis to develop a decision tree showed that our model reached moderate diagnostic power in differentiating between older adults who are cognitively normal (AUC = 0.77) and those with AD (AUC = 0.72).

INTERPRETATION

The plasma levels of arginine and valeryl carnitine, together with subject age, are promising as biomarkers for the diagnosis of AD in older adults.

摘要

目的

本研究旨在鉴定处于阿尔茨海默病(AD)早期和进展阶段患者中表达水平改变的代谢物。

方法

所有研究参与者均接受了基因筛查,并在进行代谢组学分析之前,通过神经心理学评估和淀粉样蛋白成像进行了诊断。根据这些评估,将患者分为正常组(n=15)、轻度认知障碍组(n=10)和 AD 组(n=15)。

结果

使用靶向代谢组学方法,我们发现,处于 AD 早期和进展阶段的患者的血浆 C3、C5 和 C5-DC 酰基肉碱、精氨酸、苯丙氨酸、肌酐、对称二甲基精氨酸(SDMA)和磷脂酰胆碱 ae C38:2 的水平明显改变。我们基于决策树创建了一个包含三个主要参数(年龄、精氨酸和 C5 血浆浓度)的预测模型。该模型可将 AD 患者与其他参与者区分开来,敏感性为 60%,特异性为 86.7%。对于健康对照者,敏感性为 85.7%,特异性为 61.5%。用于开发决策树的多变量 ROC 分析表明,我们的模型在区分认知正常的老年人(AUC=0.77)和 AD 患者(AUC=0.72)方面具有中等的诊断能力。

结论

精氨酸和戊酰肉碱的血浆水平与受试者年龄一起,有望成为老年 AD 诊断的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed3b/6414491/d47fc7895707/ACN3-6-537-g001.jpg

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