Evidence map›Paper›PMID 42850312›Full record

ArticleNature neuroscience2026

Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.

Yuan Hou, Yichen Li, Pengyue Zhang, Noah Lorincz-Comi, Dhruv Gohel, Fan Fan, Yunguang Qiu, Jun Yang, Xin Chen, Wenqiang Song and 27 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature neuroscience, 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

37 authors.

Yuan Hou *Cleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Yichen Li *Cleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0009-0005-1355-5018
Pengyue Zhang *Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, IN, USA.
Noah Lorincz-ComiCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Dhruv GohelCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Fan FanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Yunguang QiuCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-5094-0936
Jun YangDepartment of Entomology and Nematology, UCDMC Comprehensive Cancer Center, University of California, Davis, Davis, CA, USA.
Xin ChenCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Wenqiang SongCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Xiaoyu YangCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Zhibing TanCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Zhigang LiuCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Xing FangDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Isabela Rivera PazCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
William MartinCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Yayan FengDepartment of Genomic Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Yadi ZhouCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Jielin XuCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Lijun DouDepartment of Genomic Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Jane BorderDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Huawei ZhangDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Jena' N MaziqueDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Sung Hee HwangDepartment of Entomology and Nematology, UCDMC Comprehensive Cancer Center, University of California, Davis, Davis, CA, USA.
Richard J RomanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Tousi BabakLou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Lynn BekrisDepartment of Genomic Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA.
Ehud KaravaniAI for Accelerated Healthcare and Life Sciences Department, IBM Research - Israel, Haifa, Israel.ORCID http://orcid.org/0000-0002-0187-5437
Michael DanzigerAI for Accelerated Healthcare and Life Sciences Department, IBM Research - Israel, Haifa, Israel.ORCID http://orcid.org/0000-0002-2674-0109
Michal Rosen-ZviAI for Accelerated Healthcare and Life Sciences Department, IBM Research - Israel, Haifa, Israel.
Jonathan L HainesCleveland Institute for Computational Biology and Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Haiyuan YuWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Bruce D HammockDepartment of Entomology and Nematology, UCDMC Comprehensive Cancer Center, University of California, Davis, Davis, CA, USA.
James B LeverenzLou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Andrew A PieperBrain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Jeffrey CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, Las Vegas, NV, USA.
Feixiong ChengCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH, USA. chengf@ccf.org.ORCID http://orcid.org/0000-0002-1736-2847

Funding

Translational and Therapeutics CoreP30AG072959 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI JAGAN AYYAPPAN PILLAI · 2021 to 2026
$23.9M
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
Dark GPCR signaling underlying the Microbiome-Gut-Brain Axis for Alzheimer's Disease and Related DementiaRF1NS133812 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK, CHENG, FEIXIONG · 2023 to 2023
$2.3M
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) RF1NS133812U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P30AG072959U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R35AG71476, R25 AG083721-01U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG073323
6 · The paper itself

Abstract

Despite prolific genomic data from individuals with Alzheimer's disease (AD), translation into treatments has lagged. Here we applied Mendelian randomization to multiple AD genome-wide association studies and functional multiomics datasets to nominate druggable targets, identifying 19 targets for individuals of European ancestry and 7 for African ancestry. This included epoxide hydrolase 2 (EPHX2), for which we identified a protective missense variant (p.Arg287Gln). Experiments in induced pluripotent stem cell-derived neurons and cerebral organoids from patients with AD validated the protective role of p.Arg287Gln via reduced levels of EPHX2 and phosphorylated tau (pTau-181). Pharmacological inhibition of EPHX2 improved cognitive performance in the 5xFAD mouse model of AD. Finally, by leveraging electronic health data from 111,680 patients with mild cognitive impairment, we identified 12 drugs associated with reduced AD incidence, including trazodone (targeting ADRA1A) and baclofen (targeting GABBR1). Thus, integrating multiomics data, functional validation and electronic health data identifies new approaches for treating AD.

Identifiers

PMID42850312

What Socratic holds

Textmetadata
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.