ArticlePloS one2015
Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer's disease.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Kynurenine pathway dysregulation in cognitive impairment and dementia: a systematic review and meta-analysis.GeroScience · 2026Pooled it
- Metabolomics in the Development and Progression of Dementia: A Systematic Review.Frontiers in neuroscience · 2019Pooled it
- High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS.Journal of the American Heart Association · 2025Trial
- Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.Translational neurodegeneration · 2023Trial
- Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.Scientific reports · 2019Trial
- Personalized whole-body modeling links gut microbiota to metabolic perturbations in Alzheimer's disease.Gut microbes · 2026Article
- Omics-driven strategies for identifying biomarkers in Alzheimer's disease.Metabolic brain disease · 2026Review
- Serum amino acid levels are associated with brain hypometabolism in patients across the Alzheimer's disease continuum.IBRO neuroscience reports · 2026Article
- Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer's Disease.Metabolites · 2026Article
- The metabolic layer of cognition: integrating metabolomics, breathomics, and systems neuroscience.Frontiers in neuroscience · 2026Review
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- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
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- Investigating prolactin-induced protein and its role in modulating the metabolic state of the keratoconus microenvironment.Experimental eye research · 2025Review
- The early diagnosis of Alzheimer's disease: Blood-based panel biomarker discovery by proteomics and metabolomics.CNS neuroscience & therapeutics · 2024Review
- Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium.Biomolecules · 2024Article
- Reduction of spermine synthase enhances autophagy to suppress Tau accumulation.Cell death & disease · 2024Article
- Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models.Scientific reports · 2024Article
- Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.Obesity surgery · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.