A Nuclear Magnetic Resonance Spectroscopy Method in Characterization of Blood Metabolomics for Alzheimer’s Disease

Abstract

There is currently a crucial need for improved diagnostic techniques and targeted treatment methods for Alzheimer’s disease (AD), a disease which impacts millions of elderly individuals each year. Metabolomic analysis has been proposed as a potential methodology to better investigate and understand the progression of this disease. In this report, we present our AD metabolomics results measured with high resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) on human blood plasma samples obtained from AD and non-AD subjects. Our study centers on developments of AD and non-AD metabolomics differentiating models with procedures of quality assurance (QA) and quality control (QC) through pooled samples. Our findings suggest that analysis of blood plasma samples using HRMAS NMR has the potential to differentiate between diseased and healthy subjects, which has important clinical implications for future improvements in AD diagnosis methodologies.

1H NMR-Based Metabolomics Reveals the Intrinsic Interaction of Age, Plasma Signature Metabolites, and Nutrient Intake in the Longevity Population in Guangxi, China

“…Levels of tyrosine and valine are lower in the plasma of cancer patients relative to the levels in healthy controls [9]. In addition, a previous study reported lower blood concentrations of valine in subjects with Alzheimer's disease compared with the levels in healthy controls [11]. In the present study, the levels of tyrosine and valine were higher in participants from the LR, whereas the levels of alanine were lower compared with the levels in NLRE residents.…”

“…1 H NMR spectroscopy has high clinical significance, since metabolomic profiling can be easily conducted using peripheral tissue, plasma, fecal, and urine samples. Numerous studies have explored the profile of metabolites in serum, plasma, saliva, and urine and their association with diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer [9][10][11]. Metabolite profiles are associated with health and biological aging in humans [12].…”

Designing a quality assurance process for quality control of nuclear magnetic resonance metabolomics studies of human blood

“…To produce a high‐resolution NMR spectrum, HRMAS NMR only requires 1~10 microliters of blood, in the form of either serum or plasma, with minimal sample preparation, and a few minutes for a direct measurement, which can occur either locally or remotely. Considering these advantages, the analysis of human blood via HRMAS NMR has been utilized to develop metabolomics screening tools for human diseases, 8,9 and was discussed in a recent review 4 …”

“…To produce a high-resolution NMR spectrum, HRMAS NMR only requires 1$10 microliters of blood, in the form of either serum or plasma, with minimal sample preparation, and a few minutes for a direct measurement, which can occur either locally or remotely. Considering these advantages, the analysis of human blood via HRMAS NMR has been utilized to develop metabolomics screening tools for human diseases, 8,9 and was discussed in a recent review. 4 To advance this technology from preclinical research to potential clinical implementation, clinical NMR-based metabolomics, including HRMAS NMR, must be systematically evaluated by quantifying its consistency and reproducibility, including tasks associated with quality assurance (QA) and quality control (QC), 10 as reviewed and discussed in this Special Issue by Maroli and Powers.…”

NMR-based metabolomics in Alzheimer’s disease research: a review

“…Going from tissues to biofluids, NMR-based metabolomics of blood derivatives (plasma or serum) has shown the potential to distinguish patients with AD from CTR with optimal results ( Kim et al, 2017 ; Yilmaz et al, 2020b ; Di Costanzo et al, 2020 ; Berezhnoy et al, 2022 , Berezhnoy et al, 2023 ; Weng et al, 2022 ; Botello-Marabotto et al, 2023 ). Among metabolites (which include amino acids, carbohydrates, lipids, choline-derived metabolites, keto acids, and fatty acids) and lipoproteins (fraction and subfractions) identified and quantified in the studies, several metabolites and 2 lipoprotein subfraction of LDL cholesterol ( Table 1 ) were described as differentially abundant between AD and CTR.…”