ArticleAlzheimer's research & therapy2017
One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.
Article in Alzheimer's research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- The Relationship between Whole-Grain Intake and Measures of Cognitive Decline, Mood, and Anxiety-A Systematic Review.Advances in nutrition (Bethesda, Md.) · 2023Pooled it
- Blood levels of circulating methionine components in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.Frontiers in aging neuroscience · 2022Pooled it
- Association of Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms with Mild Cognitive Impairment Susceptibility: A Systematic Review and Meta-Analysis.Behavioural neurology · 2021Pooled it
- Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults.Journal of Alzheimer's disease : JAD · 2023Trial
- Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial.European journal of nutrition · 2021Trial
- Betaine Attenuates Hyperhomocysteinemia-Induced Cognitive Impairment by Suppressing Oxidative Stress and Activating the PI3K/AKT/GSK-3β Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Higher Serum Levels of Propionylcarnitine and Methionine are Associated with Reduced Cortical Amyloid Burden in Alzheimer's Disease.Journal of molecular neuroscience : MN · 2026Article
- Metabolomic Relationships Between Lung Cancer and Alzheimer's Disease Using Serum Nuclear Magnetic Resonance Spectroscopy.NMR in biomedicine · 2026Article
- CSF metabolomic signature during therapy for childhood acute lymphoblastic leukemia predicts subsequent working memory impairment.Molecular medicine (Cambridge, Mass.) · 2025Article
- Association of MTHFR C677T and A1298C Polymorphisms in Metabolic Alterations, Neuroimaging, and Cognitive Decline in Alzheimer's Disease: Case-Control and Bioinformatics Insights.Molecular neurobiology · 2025Article
- Unraveling Homocysteine's Role in Dementia: No Specific Association with Alzheimer's Disease, but a Connection to White Matter Hyperintensities.Aging and disease · 2025Observational
- Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium.Biomolecules · 2024Article
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.International journal of molecular sciences · 2024Review
- Cognitive Function After Stopping Folic Acid and DHA Intervention: An Extended Follow-Up Results from the Randomized, Double Blind, Placebo-Controlled Trial in Older Adults with Mild Cognitive Impairment.Journal of Alzheimer's disease reports · 2024Article
- Role of Vitamin B in Healthy Ageing and Disease.Sub-cellular biochemistry · 2024Review
- Article
- Methyl donor supplementation reduces phospho-Tau, Fyn and demethylated protein phosphatase 2A levels and mitigates learning and motor deficits in a mouse model of tauopathy.Neuropathology and applied neurobiology · 2023Article
- NMR-Based Metabolomics to Analyze the Effects of a Series of Monoamine Oxidases-B Inhibitors on U251 Cells.Biomolecules · 2023Article
- Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults.
methodsCross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ
resultsThe diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ
conclusionsWe observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers.
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Registered trials
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.