ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2022
Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Recent advances in the bioanalysis of acylcarnitines: Methodologies, challenges, and clinical perspectives.Pharmaceutical science advances · 2026Review
- Metabolic profile association with white matter hyperintensity in patients with mild cognitive impairment.IBRO neuroscience reports · 2026Article
- lncRNAInternational journal of molecular medicine · 2026Article
- Multi-omics integration of transcriptomics and metabolomics with machine learning uncovers novel risk factors for Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.Brain : a journal of neurology · 2026Article
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Multilayer Proteome and Metabolome-Based Validation Uncovers Combined Regulatory Roles and Predictive Values of 6 RNA Modifications and Cellular Senescence in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Exploring Acylcarnitine Metabolism Using Reverse Metabolomics.Analytical chemistry · 2026Article
- Nobiletin Modulates Transcriptomic and Metabolomic Alterations in Aβ42-Induced Primary Rat Astrocytes: Implications for Alzheimer's Disease.Molecular neurobiology · 2026Article
- Diet-Dependent Cognitive Benefits of Exogenous Ketone Body Precursor, (R,S)-1,3,-Butanediol, in a Mouse Model of Tauopathy.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Transglutaminase and its role in Alzheimer's disease: focus on mitochondria, aging, defective mitophagy, synaptic degeneration, and metabolomics.GeroScience · 2026Review
- Integrating polygenic and transcriptional risk scores for detecting Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Immune-proteo-metabolomic changes link to Aβ and tau pathology in Alzheimer disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus.Aging cell · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 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
- Immunometabolism Reframes Alzheimer's Disease: From Systemic Dysmetabolism to Glial Rewiring.Cellular and molecular neurobiology · 2026Review
- Rethinking on bile acid-brain axis: decoding neurotoxic and neuroprotective landscape in aging and Alzheimer's disease.Biogerontology · 2026Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 9 institutions in 3 countries.
Funding
Abstract
Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD-specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, and proteomic data in AD. Metabolite co-expression network analysis of the blood metabolomic data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) shows short-chain acylcarnitines/amino acids and medium/long-chain acylcarnitines are most associated with AD clinical outcomes, including episodic memory scores and disease severity. Integration of the gene expression data in both the blood from the ADNI and the brain from the Accelerating Medicines Partnership Alzheimer's Disease (AMP-AD) program reveals ABCA1 and CPT1A are involved in the regulation of acylcarnitines and amino acids in AD. Gene co-expression network analysis of the AMP-AD brain RNA-seq data suggests the CPT1A- and ABCA1-centered subnetworks are associated with neuronal system and immune response, respectively. Increased ABCA1 gene expression and adiponectin protein, a regulator of ABCA1, correspond to decreased short-chain acylcarnitines and amines in AD in the ADNI. In summary, our integrated analysis of large-scale multiomics data in AD systematically identifies novel metabolites and their potential regulators in AD and the findings pave a way for not only developing sensitive and specific diagnostic biomarkers for AD but also identifying novel molecular mechanisms of AD pathogenesis.
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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.