Evidence map›Paper›PMID 42328930›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.

Youjie Zeng, Noah Cook, Chenyu Yang, Sathesh K Sivasankaran, Masashi Fujita, Zachary A Gardell, Yann Le Guen, Daichi Shigemizu, Kouichi Ozaki, Takashi Morizono and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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. Article
4 · The record

Corrections and comments

  • Update of
    2025
5 · Who and what money

Authors and funding

20 authors.

Youjie ZengDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0000-0003-3842-1815
Noah CookDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0009-0006-7906-5924
Chenyu YangDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0009-0003-2017-6134
Sathesh K SivasankaranDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0000-0003-3037-6001
Masashi FujitaCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
Zachary A GardellGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California, USA.
Yann Le GuenQuantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, California, USA.
Daichi ShigemizuMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Kouichi OzakiMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Takashi MorizonoMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Norikazu HaraDepartment of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Akinori MiyashitaDepartment of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Takeshi IkeuchiDepartment of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Cyril PottierDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Carlos CruchagaNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA.
Valerio NapolioniSchool of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Macerata, Italy.
M Ryan CorcesGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California, USA.
Vilas MenonCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
Michael D GreiciusDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Michael E BelloyDepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID https://orcid.org/0000-0001-7748-9033

Funding

Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Elucidating sex-specific risk for Alzheimer's disease through state-of-the-art genetics and multi-omicsR00AG075238 · NIA · WASHINGTON UNIVERSITY · PI BELLOY, MICHAEL · 2024 to 2025
$727k
Japan Foundation for Aging and Health JP25dk0207060Knight Family Early Stage Investigator ProgramNIA NIH HHS R00AG075238NIGMS NIH HHS T32 GM136547
6 · The paper itself

Abstract

introductionGenetics studies can identify drug targets that counteract the effects of the apolipoprotein E ε4 allele (APOE*4) on Alzheimer's disease (AD) but have remained limited in power and crucially did not assess genetic findings with regard to APOE*4's cell-type-specific impact on pathobiology.

methodsWe conducted a novel APOE*4-stratified genome-wide association study (GWAS) of AD (N = 447,669) and integrated results with brain cell-type-specific multi-omics data to identify APOE*4 and cell-type-specific AD genes, followed by compound and drug repurposing.

resultsIn APOE*4 non-carriers (APOE*4-) and carriers (APOE*4+), we respectively identified 33 and 11 cell type-gene pairs with strong prioritization support. Oligodendrocytes displayed the largest proportion of APOE*4+ genes. Several genes were druggable and pinpointed APOE*4-stratified drugs or compounds. DISCUSSION: We identified a set of APOE*4-stratified genes that may be causal for AD through brain cell-type-specific mechanisms. We additionally identified compounds that may shed light on therapeutic avenues for treating AD based on an individual's APOE*4 status.

Indexed as

Alzheimer DiseaseApolipoprotein E4Genetic Predisposition to DiseaseBrainGenome-Wide Association StudyGenomicsHumansApolipoprotein E4Alzheimer's diseaseapolipoprotein Ecell‐type‐specific transcriptome‐wide association studychromatin accessibilitydifferential gene expressiondrug targetgene prioritizationgenetic colocalizationgenome‐wide association studysummary‐based Mendelian randomization

Identifiers

PMID42328930
PMCPMC13285033

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.