Alterations in Glycerolipid and Fatty Acid Metabolic Pathways in Alzheimer's Disease Identified by Urinary Metabolic Profiling: A Pilot Study

Abstract

An easily accessible and non-invasive biomarker for the early detection of Alzheimer's disease (AD) is needed. Evidence suggests that metabolic dysfunction underlies the pathophysiology of AD. While urine is a non-invasively collectable biofluid and a good source for metabolomics analysis, it is not yet widely used for this purpose. This small-scale pilot study aimed to examine whether the metabolic profile of urine from AD patients reflects the metabolic dysfunction reported to underlie AD pathology, and to identify metabolites that could distinguish AD patients from cognitively healthy controls. Spot urine of 18 AD patients (AD group) and 18 age- and sex-matched, cognitively normal controls (control group) were analyzed by mass spectrometry (MS). Capillary electrophoresis time-of-flight MS and liquid chromatography–Fourier transform MS were used to cover a larger range of molecules with ionic as well as lipid characteristics. A total of 304 ionic molecules and 81 lipid compounds of 12 lipid classes were identified. Of these, 26 molecules showed significantly different relative concentrations between the AD and control groups (Wilcoxon's rank-sum test). Moreover, orthogonal partial least-squares discriminant analysis revealed significant discrimination between the two groups. Pathway searches using the KEGG database, and pathway enrichment and topology analysis using Metaboanalyst software, suggested alterations in molecules relevant to pathways of glycerolipid and glycerophospholipid metabolism, thermogenesis, and caffeine metabolism in AD patients. Further studies of urinary metabolites will contribute to the early detection of AD and understanding of its pathogenesis.

Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer’s disease

“…The results also suggested significant alterations in glycerophospholipids and glycerolipids for APP/PS1 mice, such as PCs, LPCs, PEs, LPEs, PIs, LPIs, and TGs. Glycerol 3-phosphate, a key molecule in the initial step of glycerolipid and glycerophospholipids metabolism, was significantly lower in APP/PS1 mice when compared with WT group, which is in agreement with a recent research ( Watanabe et al, 2021 ). Previously published researches supported possible associations between glycerophospholipids and amyloid deposits related to pathology of AD ( Whiley et al, 2014 ).…”

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer’s disease

“…2020) used LASSO and SVM as well as logistic regression to construct diagnostic models (AD-CN, AD-MCI, MCI-CN) and achieved 3 AUC more than 0.9. Capryloylglycine (Zhang et al, 2022), caffeine and paraxanthine (Watanabe et al, 2021) were also found to be downregulated in AD samples which were consistent with our results. Unfortunately, our results failed to match with previous diagnostic metabolites.…”

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease

“…The use of urine metabolomics, as a non-invasively collectable biofluid, in the context of AD and the identification of early markers of AD could be crucial to developing successful therapies 36 , 37 . Notably, urinary formate has been already suggested as a new potential biomarker for Alzheimer’s disease by an independent study 14 .…”

“…Taken together, our analyses point towards altered gut microbiome secretion capacities and host-microbiome interactions on formate production, results that could help understand the crosstalk between host and microbiome metabolisms in AD. The use of urine metabolomics, as a non-invasively collectable biofluid, in the context of AD and the identification of early markers of AD could be crucial to developing successful therapies 36,37 . Notably, urinary formate has been already suggested as a new potential biomarker for Alzheimer's disease by an independent study 14 .…”