Evidence map›Paper›PMID 42506875›Full record

ArticleBriefings in bioinformatics2026

Screening of cell-type-specific meta-programs for drug repurposing in Alzheimer's disease.

Chunlong Zhang, Yuxi Zhang, Zhiyi Wu, Yuting Zhang, Fei Xue, Qinglong Tan, Xiaoling Zhong, Yu Zhang, Ziyan Zhao, Yunyi Peng and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Briefings in bioinformatics, 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

13 authors.

Chunlong ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.ORCID 0000-0002-1164-8182
Yuxi ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Zhiyi WuCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Yuting ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Fei XueCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Qinglong TanCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Xiaoling ZhongCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Yu ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Ziyan ZhaoCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Yunyi PengCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.
Hongping ChenDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150081, China.
Feng LiCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.ORCID 0009-0008-9589-9149
Yunpeng ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China.ORCID 0000-0002-3709-3656

Funding

National Natural Science Foundation of China 62472131National Science and Technology Major Program 2024ZD0530500Natural Science Foundation of Heilongjiang Province LH2023C062
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by complex cellular changes. To identify transcriptional signatures involved in AD pathology, we first analyzed nine single-cell/nucleus RNA-seq datasets from 67 high-pathology cases (Braak stages V/VI), generating an atlas of 363 243 cells. Using a multi-sample integration strategy, we identified 51 cross-sample meta-programs (MPs) across seven cell types that collectively capture key AD-related processes, including synaptic dysfunction and neuroinflammation. By screening bulk transcriptomes from 1208 ad and 725 normal samples, we found that 26 MPs (13 pathogenic and 13 protective) displayed differential activity in AD, characterized by up-regulation of microglia MPs and down-regulated of neuron MPs. Furthermore, spatial transcriptomics revealed that these MPs form spatially coherent communities associated with distinct cellular neighborhoods. Finally, we performed an integrative drug repurposing screen to identify candidate drugs predicted to regulate pathogenic MPs. In conclusion, we conducted an integrated multi-omics study to identify AD cell-type-specific MPs, and this framework can be applied to deconvolve cellular heterogeneity and screen candidate drugs for AD.

Indexed as

Alzheimer DiseaseBrainDrug RepositioningSpatial TranscriptomicsAlgorithmsAtlases as TopicFemaleGene Expression ProfilingHumansMaleMicrogliaProtein Interaction MapsSingle-Cell Gene Expression AnalysisTranscription, GeneticUnsupervised Machine LearningAlzheimer’s diseasemeta-programmulti-omicssingle cell/nucleus RNA sequencing

Identifiers

PMID42506875
PMCPMC13403181

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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.