Evidence map›Paper›PMID 40931996›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Metabolic dysregulation in Alzheimer's disease: A brain metabolomics approach.

Anke Hüls, Youran Tan, Emma Casey, Zhenjiang Li, Marla Gearing, Allan I Levey, James J Lah, Aliza P Wingo, Dean P Jones, Douglas I Walker and 2 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Adversarial random forests for omics synthesis.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Metabolic dysregulation in Alzheimer's disease: A brain metabolomics approach.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Anke HülsDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.ORCID 0000-0002-6005-417X
Youran TanGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Emma CaseyDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Zhenjiang LiGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Marla GearingGoizueta Alzheimer's Disease Research Center, School of Medicine, Emory University, Atlanta, Georgia, USA.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, School of Medicine, Emory University, Atlanta, Georgia, USA.
James J LahGoizueta Alzheimer's Disease Research Center, School of Medicine, Emory University, Atlanta, Georgia, USA.
Aliza P WingoDepartment of Psychiatry, University of California, Davis, Sacramento, California, USA.
Dean P JonesDepartment of Medicine, Emory University, Atlanta, Georgia, USA.
Douglas I WalkerGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Thomas S WingoDepartment of Neurology, University of California, Davis, Sacramento, California, USA.
Donghai LiangDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.ORCID 0000-0001-7311-2298

Funding

Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI Melanie Alice PEARSON · 2013 to 2026
$22.6M
IMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related DementiasU01AG088425 · NIA · EMORY UNIVERSITY · PI Anke Huels, Donghai Liang · 2024 to 2026
$6.8M
Air pollution and early signs of dementiaR01AG079170 · NIA · EMORY UNIVERSITY · PI Anke Huels, Thomas Spurgeon Wingo · 2022 to 2026
$3.6M
Air pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementiasR01AG087250 · NIA · EMORY UNIVERSITY · PI Anke Huels, Donghai Liang · 2024 to 2026
$2.3M
The Omics and Mixtures Integration on Traffic exposure and Preterm Birth (OMIT-PTB) StudyR01ES035738 · NIEHS · EMORY UNIVERSITY · PI Donghai Liang · 2024 to 2026
$2.0M
Traffic Exposure, Maternal Metabolome and Birth Outcomes Study (TEMMBO Study)R21ES032117 · NIEHS · EMORY UNIVERSITY · PI LIANG, DONGHAI · 2021 to 2022
$420k
NIA NIH HHS P30AG055611NIA NIH HHS R01 AG079170NIA NIH HHS R01AG079170NIA NIH HHS R01 AG087250NIA NIH HHS R01AG087250NIA NIH HHS U01 AG088425NIA NIH HHS U01AG088425NIEHS NIH HHS P30 ES019776NIEHS NIH HHS P30ES019776NIEHS NIH HHS R01 ES035738NIEHS NIH HHS R01ES035738NIEHS NIH HHS R21 ES032117NIEHS NIH HHS R21ES032117Rollins School of Public Health Dean's Pilot and Innovation
6 · The paper itself

Abstract

introductionThis study aimed to identify specific biological pathways and molecules involved in Alzheimer's disease (AD) neuropathology.

methodsWe conducted cutting-edge high-resolution metabolomics profiling of 162 human frontal cortex samples from the Emory Alzheimer's Disease Research Center (ADRC) brain bank with comprehensive neuropathological evaluations.

resultsWe identified 155 unique metabolic features and 36 pathways associated with three well-established AD neuropathology markers. Of these, 18 novel metabolites were confirmed with level 1 evidence, implicating their involvement in amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and metabolism of cofactors and vitamins in AD neuropathology. Genetic variability influenced these associations, with non-carriers of the apolipoprotein E (APOE) ε4 allele showing stronger perturbations in metabolites including glucose and adenosine 5'-diphosphoribose. DISCUSSION: This study demonstrates the potential of high-resolution metabolomic profiling in brain tissues to elucidate molecular mechanisms underlying AD pathology. Our findings provide critical insights into metabolic dysregulation in AD and its interplay with genetic factors. HIGHLIGHTS: This is one of the largest untargeted metabolomics studies of human brain tissue. 155 metabolic features, and 36 metabolic pathways were linked to Alzheimer's disease (AD) neuropathology. Of these, 18 unique metabolites were confirmed with level 1 evidence. Glucose and adenosine 5'-diphosphoribose identified as key metabolic alterations in AD.

Indexed as

Alzheimer DiseaseBrainMetabolomicsAgedAged, 80 and overApolipoprotein E4FemaleHumansMaleApolipoprotein E4Alzheimer's diseaseamino acid metabolismcarbohydrate metabolismhigh‐resolution metabolomicslipid metabolismmetabolism of cofactors and vitaminsneuropathologynucleotide metabolismuntargeted metabolomics

Identifiers

PMID40931996
PMCPMC12423944

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.