Evidence map›Paper›PMID 42094052›Full record

ArticleResearch square2026

DEVELOPMENT AND APPLICATION OF BRAIN TISSUE BASED MULTI-OMICS PROFILE SCORES FOR ALZHEIMER'S DISEASE.

Timur Tug, Donghai Liang, Sven Teschke, Youran Tan, Marla Gearing, Allan I Levey, James J Lah, Aliza P Wingo, Thomas S Wingo, Michael Lau and 2 more

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Timur TugDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Donghai LiangDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Sven TeschkeDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Youran TanGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Marla GearingDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Allan I LeveyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
James J LahDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Aliza P WingoDepartment of Psychiatry, University of California, Davis, Sacramento, CA USA.
Thomas S WingoDepartment of Neurology, University of California, Davis, Sacramento, CA USA.
Michael LauMathematical Institute, Heinrich Heine University, Düsseldorf, Germany.
Katja IckstadtDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Anke HülsDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Funding

Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI William Michael Caudle · 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 R01 AG079170NIA NIH HHS R01 AG087250NIA NIH HHS U01 AG088425NIEHS NIH HHS P30 ES019776NIEHS NIH HHS R01 ES035738NIEHS NIH HHS R21 ES032117
6 · The paper itself

Abstract

backgroundAdvances in omics technologies, such as epigenomics and metabolomics, provide novel insights into the biological mechanisms underlying Alzheimer's disease (AD). However, little is known how different omics layers interact and jointly relate to AD neuropathology.

methodsWe performed a comprehensive single- and multi-omics analysis integrating genome-wide DNA methylation and high-resolution metabolomics data from 157 frontal cortex samples. We developed novel single and multi-omics profile scores (PS) for AD pathology, using a combination of machine learning, regression, and pathway analysis.

resultsFor the ABC score (Amyloid, Braak, CERAD) the PS of DNAm outperformed metabolomics-based PS (median R†: 0.11 vs. 0.04). Combining both omics layers with the best-performing multi-omics PS yielded a partial R† of 0.15 for the ABC score independent of age, sex, race and socioeconomic factors. DNAm-specific pathways highlighted redox balance, immune activation, synaptic signaling, and lipid biosynthesis, whereas metabolomics-specific pathways emphasized inflammatory, hormonal, lipid, and energy metabolism. Notably, both omics layers converged on lipid metabolism and signal transduction as shared biological systems implicated in AD neuropathology.

conclusionsDespite limited gains in predictive accuracy, integrative pathway and network analyses of DNAm and metabolomics PS converged on lipid metabolism and signal transduction, underscoring shared biological mechanisms and the value of multi-omics approaches for biological insight rather than prediction alone.

Indexed as

Alzheimer’s diseaseDNA methylationmachine learningmetabolomicsmulti-omicsneuropathologyprofile scores

Identifiers

PMID42094052
PMCPMC13142619

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.