ArticleScientific reports2024
Risk of Alzheimer's disease and genetically predicted levels of 1400 plasma metabolites: a Mendelian randomization study.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Investigating causal associations among inflammatory proteins, blood metabolites, and Alzheimer's disease risk.BMC psychiatry · 2026Article
- Potential Protection Against Parkinson's Disease by Ergothioneine-Nature's Multifactorial Neuroprotectant.Antioxidants (Basel, Switzerland) · 2026Review
- 3,4-Dihydroxybenzaldehyde Exerts Anti-Alzheimer's Effects by Inhibiting Aβ Protofibril Assembly and Activating Antioxidant Defense Mechanisms.International journal of molecular sciences · 2026Article
- Oral microbiome-metabolome axis links glycerophospholipid dysregulation to Alzheimer's disease.Journal of oral microbiology · 2026Article
- Elucidating the causal effects of plasma metabolites on breast cancer from multiple perspectives.International journal of surgery (London, England) · 2026Article
- BrainGeneBot: a framework for variant prioritization and generative pretrained transformer-informed interpretation across polygenic risk score studies.Briefings in bioinformatics · 2025Article
- Genetically instrumented circulating metabolites and hepatobiliary cancer risk: A multi-tiered Mendelian randomization and functional interrogation.Frontiers in oncology · 2025Article
- The Current Situation and Future Trends of Ergothioneine in Biology and Medical Research: A Bibliometric Analysis.Journal of multidisciplinary healthcare · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
Alzheimer's disease (AD) is a metabolic disorder. Discovering the metabolic products involved in the development of AD may help not only in the early detection and prevention of AD but also in understanding its pathogenesis and treatment. This study investigated the causal association between the latest large-scale plasma metabolites (1091 metabolites and 309 metabolite ratios) and AD. Through the application of Mendelian randomization analysis methods such as inverse-variance weighted (IVW), MR-Egger, and weighted median models, 66 metabolites and metabolite ratios were identified as potentially having a causal association with AD, with 13 showing significant causal associations. During the replication validation phase, six metabolites and metabolite ratios were confirmed for their roles in AD: N-lactoyl tyrosine, argininate, and the adenosine 5'-monophosphate to flavin adenine dinucleotide ratio were found to exhibit protective effects against AD. In contrast, ergothioneine, piperine, and 1,7-dimethyluric acid were identified as contributing to an increased risk of AD. Among them, argininate showed a significant effect against AD. Replication and sensitivity analyses confirmed the robustness of these findings. Metabolic pathway analysis linked "Vitamin B6 metabolism" to AD risk. No genetic correlations were found, but colocalization analysis indicated potential AD risk elevation through top SNPs in APOE and PSEN2 genes. This provides novel insights into AD's etiology from a metabolomic viewpoint, suggesting both protective and risk metabolites.
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Registered trials
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