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

Overview

Authors: Youjie Zeng1,2, Noah Cook1,2, Chenyu Yang1,2, Sathesh K Sivasankaran1,2, Masashi Fujita3, Zachary A Gardell4,5,6, Yann Le Guen7, Daichi Shigemizu8,9, Kouichi Ozaki8,9,10,11, Takashi Morizono8, Norikazu Hara12, Akinori Miyashita12, Takeshi Ikeuchi12, Cyril Pottier1,2, Carlos Cruchaga2,13, Valerio Napolioni14, M Ryan Corces4,5,6, Vilas Menon3, Michael D Greicius15, Michael E Belloy1,2
ORCID iDs: Youjie Zeng, Noah Cook, Chenyu Yang, Sathesh K Sivasankaran, Michael E Belloy
15 affiliations
  1. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA
  2. NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA
  3. Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
  4. Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California, USA
  5. Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, California, USA
  6. Department of Neurology, University of California San Francisco, San Francisco, California, USA
  7. Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, California, USA
  8. Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
  9. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
  10. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  11. Department of Aging Research, Nagoya University Graduate School of Medicine, Nagoya, Japan
  12. Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
  13. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
  14. School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Macerata, Italy
  15. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA
Institutions: Washington University in St. Louis (United States); Columbia University Irving Medical Center (United States); Columbia University (United States); Gladstone Institutes (United States); University of California, San Francisco (United States); Stanford Medicine (United States); Stanford University (United States); Hiroshima University (Japan); National Center for Geriatrics and Gerontology (Japan); RIKEN Center for Integrative Medical Sciences (Japan); Nagoya University (Japan); Niigata University (Japan); Università di Camerino (Italy)
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association, volume 22, issue 6, article e71552
Dates: received 5 February 2026; accepted 29 April 2026; published online 22 June 2026; in print June 2026
Type: Research article · Language: English
License: CC BY-NC-ND
Identifiers: DOI 10.1002/alz.71552 · PMID 42328930 · PMCID PMC13285033 · OpenAlex W4417152262
Open access: hybrid, a free copy (OpenAlex)
Preprint: doi:10.64898/2025.12.02.25341367
Status: data only
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Connectivity, Statistics, Smoothing, state filtering, decompositions, Machine learning
Keywords: Alzheimer's disease, apolipoprotein E, cell‐type‐specific transcriptome‐wide association study, chromatin accessibility, differential gene expression, drug target, gene prioritization, genetic colocalization, genome‐wide association study, summary‐based Mendelian randomization
MeSH: Alzheimer Disease*, Apolipoprotein E4*, Genetic Predisposition to Disease*, Brain, Genome-Wide Association Study, Genomics, Humans (* major topic)
Topic: Alzheimer's disease research and treatments (Physiology, Medicine), according to OpenAlex
Funding: National Institute on Aging (R00AG075238); NIA NIH HHS (R00AG075238); Japan Foundation for Aging and Health (JP25dk0207060); Knight Family Early Stage Investigator Program
Citations: not cited yet (Europe PMC); 73 references in the paper

Abstract

The abstract is not reproduced here: the paper's license (CC BY-NC-ND) does not allow it. Read it in the paper, at the publisher or on Europe PMC.

Code

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Data

Datasets cited

Data availability statement

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Read it in the paper: doi.org/10.1002/alz.71552.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 20 authors, 10 keywords, 7 MeSH terms, 4 funders, 71 references.

Cite

This paper

Zeng, Y., Cook, N., Yang, C., Sivasankaran, S. K., Fujita, M., Gardell, Z. A., Le Guen, Y., Shigemizu, D., Ozaki, K., Morizono, T., Hara, N., Miyashita, A., Ikeuchi, T., Pottier, C., Cruchaga, C., Napolioni, V., Corces, M. R., Menon, V., Greicius, M. D., & Belloy, M. E. (2026). APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses. Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(6), e71552. https://doi.org/10.1002/alz.71552

BibTeX

@article{zeng2026apoe,
author = {Zeng, Youjie and Cook, Noah and Yang, Chenyu and Sivasankaran, Sathesh K and Fujita, Masashi and Gardell, Zachary A and Le Guen, Yann and Shigemizu, Daichi and Ozaki, Kouichi and Morizono, Takashi and Hara, Norikazu and Miyashita, Akinori and Ikeuchi, Takeshi and Pottier, Cyril and Cruchaga, Carlos and Napolioni, Valerio and Corces, M Ryan and Menon, Vilas and Greicius, Michael D and Belloy, Michael E},
title = {{APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = jun,
volume = {22},
number = {6},
pages = {e71552},
publisher = {Wiley},
issn = {1552-5260},
doi = {10.1002/alz.71552},
url = {https://doi.org/10.1002/alz.71552},
pmid = {42328930},
pmcid = {PMC13285033}
}

RIS

TY - JOUR
AU - Zeng, Youjie
AU - Cook, Noah
AU - Yang, Chenyu
AU - Sivasankaran, Sathesh K
AU - Fujita, Masashi
AU - Gardell, Zachary A
AU - Le Guen, Yann
AU - Shigemizu, Daichi
AU - Ozaki, Kouichi
AU - Morizono, Takashi
AU - Hara, Norikazu
AU - Miyashita, Akinori
AU - Ikeuchi, Takeshi
AU - Pottier, Cyril
AU - Cruchaga, Carlos
AU - Napolioni, Valerio
AU - Corces, M Ryan
AU - Menon, Vilas
AU - Greicius, Michael D
AU - Belloy, Michael E
TI - APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses
T2 - Alzheimer's & dementia : the journal of the Alzheimer's Association
J2 - Alzheimers Dement
PY - 2026
DA - 2026/06/01
VL - 22
IS - 6
SP - e71552
SN - 1552-5260
PB - Wiley
DO - 10.1002/alz.71552
UR - https://doi.org/10.1002/alz.71552
LA - en
ER -

CSL-JSON

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