Evidence map›Paper›PMID 41642643›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.

Fuhai Li, Yike Chen, Daniel Western, Muhammad Ali, Menghan Liu, Katherine Gong, Ying Xu, Joseph Lowery, David M Holtzman, Chloe Robins and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

23 authors.

Fuhai LiInstitute For Informatics (I2), Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Yike ChenDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Daniel WesternDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Muhammad AliDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Menghan LiuDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Katherine GongDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Ying XuDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Joseph LoweryDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
David M HoltzmanDepartment of Neurology, Knight Alzheimer's Disease Research Center, Hope Center for Neurological Disorders, ., St. Louis, Missouri, USA.
Chloe RobinsHuman Genetics & Genomics, Research Technologies, GSK, Cambridge, MA, USA.
John D EicherHuman Genetics & Genomics, Research Technologies, GSK, Cambridge, MA, USA.
Yen-Ning HuangCenter For Neuroimaging, Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
ShiWei LiuCenter For Neuroimaging, Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Tamina ParkCenter For Neuroimaging, Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Andrew J SaykinCenter For Neuroimaging, Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Kwangsik NhoCenter For Neuroimaging, Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Mahdi MoqriDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Richard C MohsGlobal Alzheimer's Platform Foundation, Washington, DC, USA.
Amelia FarinasThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
Patricia Moran-LosadaThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
Hamilton Se-Hwee OhThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
Tony Wyss-CorayThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0000-0002-0276-2899

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics DiscoveryU01AG073323 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2025
$4.0M
IDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7M
AI models of multi-omic data integration for ming longevity core signaling pathwaysR33AG078799 · NIA · WASHINGTON UNIVERSITY · PI LI, FUHAI, PROVINCE, MICHAEL A. · 2025 to 2025
$1.5M
AI models of multi-omic data integration for ming longevity core signaling pathwaysR21AG078799 · NIA · WASHINGTON UNIVERSITY · PI LI, FUHAI, PROVINCE, MICHAEL A. · 2023 to 2023
$461k
Alzheimer's Association Zenith Fellows Award ZEN-22-848604Chan Zuckerberg InitiativeMichael J. Fox FoundationNIA NIH HHS P01 AG003991NIA NIH HHS R01AG044546NIA NIH HHS R21 AG078799NIA NIH HHS R33 AG078799NIA NIH HHS U01 AG073323NIH HHS 1R21AG078799-01A1(FL)NIH HHS 4R33AG078799-02(FL)NIH HHS P01AG003991(CC JCM)NIH HHS P30AG10161 (DAB)NIH HHS P30AG72975 (DAB)NIH HHS R01AG044546 (CC)NIH HHS R01AG15819 (DAB)NIH HHS R01AG17917 (DAB)NIH HHS RF1AG053303 (CC)NIH HHS RF1AG058501 (CC)NIH HHS RF1AG074007 (YJS)NIH HHS U01AG058922 (CC)NIH HHS U01AG46152 (DAB)NIH HHS U01AG61356 (DAB)
6 · The paper itself

Abstract

Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-dependent and independent effects is instrumental for understanding the biology of AD. We conducted an APOE-stratified multi-omic analysis in multiple large datasets to identify AD-associated plasma proteins and metabolites. More than 64% of the identified proteins were not found in non-APOE stratified studies, and 17% of the proteins showed APOE-specific trends. Mitochondrial dysfunction was associated in AD independently of APOE and was accompanied by disruptions in glucose and lipid metabolism and cell death and increased in inflammatory signaling activation. Lipid upregulation was found in AD cases when compared with controls with the same APOE genotype, indicating that additional factors beyond APOE affect lipid regulation and AD risk. These findings may be informative in guiding the development of effective medications for AD.

Indexed as

Alzheimer DiseaseApolipoproteins EInflammationLipid MetabolismMetabolomicsMitochondriaProteomicsFemaleHumansMaleMultiomicsApolipoproteins EalzheimerAPOEmetabolomicsproteomics

Identifiers

PMID41642643
PMCPMC13073338

What OpenQuestion 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 OpenQuestion graph.