ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2017
Metabolic network failures in Alzheimer's disease: A biochemical road map.
Open access · greenAbstract read
In one paragraph
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
271citing papers in PubMed, 4 pooled it
17.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
271 citing papers in PubMed, 4 syntheses or guidelines pooled it, 481 citations in OpenAlex.
- Kynurenine pathway dysregulation in cognitive impairment and dementia: a systematic review and meta-analysis.GeroScience · 2026Pooled it
- Pooled it
- Lipids as Early and Minimally Invasive Biomarkers for Alzheimer's Disease.Current neuropharmacology · 2022Pooled it
- A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer's disease.Frontiers in aging neuroscience · 2022Pooled it
- Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.Translational neurodegeneration · 2023Trial
- Diet Effects on Cerebrospinal Fluid Amino Acids Levels in Adults with Normal Cognition and Mild Cognitive Impairment.Journal of Alzheimer's disease : JAD · 2021Trial
- Branched-chain amino acids and gut microbiota: coregulation and impact on neurological function via the gut-brain axis.Gut microbes · 2026Review
- 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
- Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.Current research in microbial sciences · 2026Review
- Circulating Metabolite Signatures Associated With Amyloid Positivity, Cognitive Performance and Plasma P-tau181 Levels in Cognitively Unimpaired Older Adults.Molecular neurobiology · 2026Article
- Circulating lipids are related to longitudinal changes of ATN biomarkers for Alzheimer's disease.Molecular psychiatry · 2026Article
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Determining the metabolic profile measured using ultra-high pressure liquid chromatography associated with Beta Amyloid burden in the brain in individuals with mild cognitive impairment.Research square · 2026Article
- The blood metabolome of brain health in midlife and influences of genes, microbiome and exposome.Nature aging · 2026Article
- Recent Trends in Metabolomics by NMR Spectroscopy.Angewandte Chemie (International ed. in English) · 2026Review
- An imaging biomarker to detect non-glucogenic shift in brain energy metabolism in Alzheimer's disease.Journal of translational medicine · 2026Article
- Odd-Chain Fatty Acids-Enriched Algal Oil Improves Locomotor Function and Modulates Metabolic Pathways inMolecules (Basel, Switzerland) · 2026Article
- Circulating Sphingomyelins Correlate With Plasma T-Tau in Cognitively Unimpaired Older Adults at Risk of Developing Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Plasma lipid trajectories improve prediction of future Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
211 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
45 authors at 20 institutions in 7 countries.
Jon B ToledoDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: jbtoledoatucha@houstonmethodist.org.
Matthias ArnoldInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Gabi KastenmüllerInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Rui ChangDepartment of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Rebecca A BaillieRosa & Co LLC, San Carlos, CA, USA.
Xianlin HanSanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA.
Madhav ThambisettyClinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Jessica D TenenbaumDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Karsten SuhreInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Physiology and Biophysics, Weill Cornell Medical College, Qatar, Doha, Qatar.
J Will ThompsonDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Lisa St John-WilliamsDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Siamak MahmoudianDehkordiBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Daniel M RotroffBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
John R JackBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Alison Motsinger-ReifBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Shannon L RisacherDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; The Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Colette BlachDuke Molecular Physiology Institute, Duke University, Durham, NC, USA; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Joseph E LucasInstitute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
Tyler MassaroInstitute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
Gregory LouieDepartment of Psychiatry, Duke University, Durham, NC, USA; Duke Institute for Brain Sciences, Duke University, Durham, NC, USA.
Hongjie ZhuDepartment of Psychiatry, Duke University, Durham, NC, USA; Duke Institute for Brain Sciences, Duke University, Durham, NC, USA.
Guido DallmannBIOCRATES Life Sciences AG, Innsbruck, Austria.
Kristaps KlavinsBIOCRATES Life Sciences AG, Innsbruck, Austria.
Therese KoalBIOCRATES Life Sciences AG, Innsbruck, Austria.
Sungeun KimDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; The Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Kwangsik NhoDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; The Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Li ShenDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; The Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Ramon CasanovaClinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Sudhir VarmaClinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Cristina Legido-QuigleyIPS, Faculty of Life Sciences and Medicine, King's College London, London.
M Arthur MoseleyDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
Kuixi ZhuDepartment of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Marc Y R HenrionDepartment of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sven J van der LeeDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
Amy C HarmsAnalytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
Ayse DemirkanDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
Thomas HankemeierDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands; Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
Cornelia M van DuijnDepartment of Epidemiology, ErasmusMC, Rotterdam, The Netherlands; Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
John Q TrojanowskiDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Leslie M ShawDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew J SaykinDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; The Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Michael W WeinerDepartment of Radiology, Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.
P Murali DoraiswamyDepartment of Psychiatry, Duke University, Durham, NC, USA; Duke Institute for Brain Sciences, Duke University, Durham, NC, USA.
Rima Kaddurah-DaoukDepartment of Psychiatry, Duke University, Durham, NC, USA; Duke Institute for Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA. Electronic address: kaddu001@mc.duke.edu.
Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Duke University · USIndiana University – Purdue University Indianapolis · USNorth Carolina State University · USBiocrates Life Sciences (Austria) · ATIcahn School of Medicine at Mount Sinai · USErasmus University Rotterdam · NLNational Institute on Aging · USUniversity of Pennsylvania · USAnalytical Biosciences (China) · CNCenter for Child and Family Health · USCentre for Human Drug Research · NLDeutsches Diabetes-Zentrum e.V. · DEErasmus MC · NLHelmholtz Zentrum München · DEIndiana University School of MedicineInstitute of Bioinformatics and Systems Biology · DEKing's College London · GBMethodist Hospital · USNational Institutes of Health · USRosa (United States) · US
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI ANDREW J SAYKIN · 2016 to 2026
$226.7MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MResearch Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3MUPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1MProject IV: "Alpha-Synuclein Strains & Diverse Synucleinopathies"P50NS053488 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2007 to 2017
$20.9MUnderstanding mechanisms and seeking novel biomarkers in Alzheimer's diseaseZIAAG000200 · NIA · NATIONAL INSTITUTE ON AGING · PI RESNICK, SUSAN · 2013 to 2024
$12.2MMetabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0MMemory Circuitry in MCI and Early Alzheimer’s Disease Prodrome: Molecular DriversR01AG019771 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 2001 to 2021
$6.9MMetabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3MMetabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4MSTRESS AND INFLAMMATION IN THE PATHOPHYSIOLOGY OF LATE-LIFE DEPRESSIONR01MH098260 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI SHELINE, YVETTE I · 2013 to 2018
$2.4MBuilding Novel Predictive Networks for high-throughput, in-silico Key Driver Prioritization to Enhance Drug Target Discovery in AMP-AD and M2OVE-ADRF1AG057457 · NIA · UNIVERSITY OF ARIZONA · PI BRADSHAW, ELIZABETH M, CHANG, RUI · 2017 to 2019
$2.3MIntramural NIH HHS Z99 AG999999NIA NIH HHS K01 AG049050NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010133NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG046171NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG057457NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG024904NIBIB NIH HHS R01 EB022574NIMH NIH HHS R01 MH098260NINDS NIH HHS P50 NS053488NLM NIH HHS R00 LM011384NLM NIH HHS R01 LM011360NLM NIH HHS R01 LM012535
Abstract
introductionThe Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.
methodsFasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted.
resultsMultivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ DISCUSSION: Metabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.
Indexed as
AgedAged, 80 and overAgingAlzheimer DiseaseAmino AcidsAmyloid beta-PeptidesAniline CompoundsCognitive DysfunctionCohort StudiesCross-Sectional StudiesFastingFemaleHumansMaleMetabolic DiseasesMetabolic Networks and Pathways2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazoleAmino AcidsAmyloid beta-Peptidesamyloid beta-protein (1-42)Aniline CompoundsPeptide FragmentsPhosphatidylcholinesSphingomyelinstau ProteinsThiazolesAcylcarnitinesAlzheimer's diseaseBiochemical networksBiomarkersBranched-chain amino acidsDementiaMetabolismMetabolomicsMetabonomicsPharmacometabolomicsPharmacometabonomicsPhospholipidsPrecision medicineSerumSphingomyelinsSystems biology
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.