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

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 (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.

Plasma metabolomics of presymptomaticPSEN1-H163Y mutation carriers: A pilot study

“…In presymptomatic MC, amino acids, fatty acyls, carboxylic acids, hexoses, purine nucleosides, glycerophosphatidylcholines, and bile acids were significantly altered when compared to NC (Table 2). Interestingly, these classes of metabolites are also associated with sporadic AD [2,6,8,9,11,12,[29][30][31][32]. Notably, we found asparagine, propionyl-l-carnitine, glycerophosphatidylcholine species and asymmetric dimethylarginine ( Table 2), which were part of the metabolite panel that previously has been reported to predict the clinical transition from presymptomatic to prodromal or symptomatic late-onset AD [9].…”

“…Previously, several studies have described the plasma metabolic profile of sporadic mild cognitive impairment (MCI) and AD cases [2,[6][7][8][9][10][11][12]. A targeted plasma lipid profiling was performed in PSEN1 mutation carriers [13].…”

Serum Metabolomics Profiling of Commercially Mixed Functional Foods—Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy

“…In the cerebrospinal fluid (CSF), the use of biomarkers such as the Aβ level as well as magnetic resonance imaging increases the diagnostic accuracy and can be used to distinguish between different types of dementia [ 15 ]. However, in primary care and clinical studies, blood biomarkers are greatly appreciated because they are less invasive and more available compared to the other sample such as cerebrospinal fluid which is time-consuming, invasive and expensive [ 51 , 52 ]. On the other hand, the use of blood parameters has its drawback as blood parameters (Aβ and p-tau) are not the most reliable, sensitive and specific biomarkers for AD compared to CSF [ 53 ].…”

“…As mentioned before, even though the CSF sample is time-consuming, invasive and expensive [ 52 ], this biofluid is the best to determine the Aβ-42 and p-tau protein, which a combination of has a sensitivity from 90 to 95% and specificity around 85%. However, these markers are still overlapping with other types of dementia.…”

Comprehensive Metabolomic Search for Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis

“…The identification of numerous metabolites has improved the current understanding of metabolites and systems-level effects, thereby providing novel insights into the underlying mechanisms for various physiological conditions and aberrant processes, including diseases [5]. Metabolomic analysis is extensively employed to develop a set of diagnostic and prognostic biomarkers for various diseases, such as liver disease [5,6,7] and Alzheimer’s disease [8,9]; it is also applied for personalized pharmacotherapy [10]. Since HCC alters various metabolic functions of the liver, metabolomic-based biomarkers may serve as valuable tools for the early detection of HCC.…”