Evidence map›Paper›PMID 41139712›Full record

ArticleMolecular psychiatry2026

Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy.

Huihong Li, Zhiran Xie, Yuxuan Tian, Ruoyin Zhou, Yaxi Yang, Bingying Lin, Si Chen, Jie Wu, Zihan Deng, Jianwei Li and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
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  5. Article
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

16 authors.

Huihong LiDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.ORCID http://orcid.org/0009-0006-4572-7176
Zhiran XieProgram in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA.ORCID http://orcid.org/0009-0004-2235-6822
Yuxuan TianProgram in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA.
Ruoyin ZhouProgram in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA.
Yaxi YangProgram in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA.
Bingying LinDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Si ChenDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Jie WuDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.ORCID http://orcid.org/0000-0002-6039-9119
Zihan DengDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Jianwei LiDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Mingjie ChenDepartment of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China.
Xueke LiuDepartment of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China.
Yushan SunDepartment of Biotechnology and Food Engineering, Guangdong Technion - Israel Institute of Technology, Shantou, Guangdong, China.
Naili WeiDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Bing HuangDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. bhuangfd@stu.edu.cn.ORCID http://orcid.org/0000-0001-5138-1446
Xiaoyu JiDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. xyji@stu.edu.cn.ORCID http://orcid.org/0000-0003-4622-0618

Funding

National Science Foundation of China | Young Scientists Fund 82201629
6 · The paper itself

Abstract

Alzheimer's disease (AD) and epilepsy (EP) share a complex bidirectional relationship, yet the molecular mechanisms underlying their comorbidity remain insufficiently explored. To identify potential transcriptional programs across animal models and human patients with AD and EP, we conducted a comprehensive genome-wide transcriptomic analysis. Our investigation included mouse models of temporal lobe epilepsy (pilocarpine- and kainic acid-induced; n = 280), AD transgenic models (7 transgenic models expressing human tau or amyloid pathology; n = 257), and performed cross-species validation in human cohorts (EP: n = 182; AD: n = 301). We identified a highly conserved immune-related module across all models and patient cohorts. The hub consensus signatures of this module were centered around a microglial synaptic pruning pathway involving TYROBP, TREM2, and C1Q complement components. Gene regulatory network analysis identified TYROBP as the key regulatory signature. These signatures showed consistent up-regulation in both conditions and diagnostic potential. Differential expression analyses revealed their predominant expression in specific microglial subpopulations associated with complement-mediated synaptic pruning and immune activation. Neural circuit modeling further demonstrates the asymmetric sensitivity of synaptic pruning to network dynamics. Loss of inhibitory synapses has a disproportionately significant impact on neural network excitation/inhibition balance and synchronization. Our findings support microglial complement-mediated synaptic pruning as a conserved central pathway linking neurodegeneration to epileptogenesis, suggesting a promising therapeutic target for AD and EP comorbidity.

Indexed as

Alzheimer DiseaseEpilepsyAdaptor Proteins, Signal TransducingAnimalsDisease Models, AnimalEpilepsy, Temporal LobeFemaleGene Expression ProfilingGene Regulatory NetworksGenome-Wide Association StudyHumansMaleMembrane GlycoproteinsMembrane ProteinsMiceMice, TransgenicAdaptor Proteins, Signal TransducingMembrane GlycoproteinsMembrane ProteinsReceptors, Immunologictau ProteinsTREM2 protein, humanTYROBP protein, human

Identifiers

PMID41139712

What OpenQuestion holds

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Registered trials

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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.