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

• Published in: Annals of clinical and translational neurology Vol. 6; no. 3; pp. 537 - 545
• Main Authors: Lin, Chia‐Ni, Huang, Chin‐Chang, Huang, Kuo‐Lun, Lin, Kun‐Ju, Yen, Tzu‐Chen, Kuo, Hung‐Chou
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2019; John Wiley and Sons Inc
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer's disease; Apolipoproteins E - blood; Biomarkers; Biomarkers - blood; Cognitive Dysfunction; Cohort Studies; Decision trees; Female; Healthy Volunteers; Humans; Male; Metabolome; Metabolomics; Middle Aged; Older people
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.726

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 (n = 15), with mild cognitive impairment (n = 10), and with AD (n = 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.