Evidence map›Paper›PMID 41950003›Full record

ArticleCell reports2026

Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.

Lucas P Scheidemantel, Katia de Paiva Lopes, Chris Gaiteri, Vilas Menon, Philip L De Jager, Julie A Schneider, Aron S Buchman, Yanling Wang, Shinya Tasaki, Roberto T Raittz and 2 more

Abstract read
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Lucas P ScheidemantelLaboratory of Artificial Intelligence Applied to Bioinformatics, Professional and Technological Education Sector (SEPT), Federal University of Parana, Curitiba 81520-260, Brazil.
Katia de Paiva LopesLaboratory of Artificial Intelligence Applied to Bioinformatics, Professional and Technological Education Sector (SEPT), Federal University of Parana, Curitiba 81520-260, Brazil; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Chris GaiteriRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Vilas MenonCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Aron S BuchmanRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Yanling WangRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Shinya TasakiRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Roberto T RaittzLaboratory of Artificial Intelligence Applied to Bioinformatics, Professional and Technological Education Sector (SEPT), Federal University of Parana, Curitiba 81520-260, Brazil.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.
Ricardo A VialleLaboratory of Artificial Intelligence Applied to Bioinformatics, Professional and Technological Education Sector (SEPT), Federal University of Parana, Curitiba 81520-260, Brazil; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: ricardo_a_vialle@rush.edu.

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
AIM-AI: an Actionable, Integrated and Multiscale genetic map of Alzheimer's disease via deep learningU01AG079847 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Christopher A. Gaiteri, Xiaoqian Jiang · 2023 to 2026
$5.1M
NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG079847
6 · The paper itself

Abstract

The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is characterized by elevated immune activity at the epigenetic level, decreased heat shock gene expression in the transcriptome, and disrupted energy metabolism and cytoskeletal dynamics in the proteome. Unsupervised clustering reveals 11 molecular subtypes, including three AD-associated clusters displaying distinct molecular signatures and phenotypic characteristics. Our findings provide a comprehensive map of molecular mechanisms underlying AD heterogeneity, highlighting neuroinflammatory processes and yielding potential biomarkers and therapeutic targets for precision medicine approaches.

Indexed as

Alzheimer’s diseasebiomarkersCP: neuroscienceMOFAmolecular subtypesmulti-omics integration

Identifiers

PMID41950003
PMCPMC13244359

What OpenQuestion holds

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LicenceCC BY-NC
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.