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

  1. Huihong Li
  2. Zhiran Xie
  3. Yuxuan Tian
  4. Ruoyin Zhou
  5. Yaxi Yang
  6. Bingying Lin
  7. Si Chen
  8. Jie Wu
  9. Zihan Deng
  10. Jianwei Li
  11. Mingjie Chen
  12. Xueke Liu
  13. Yushan Sun
  14. Naili Wei
  15. Bing Huang
  16. Xiaoyu Ji

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Abstract

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  1. Version published to 10.1038/s41380-025-03318-0
  2. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/15682703.

    Does the introduction explain the objective of the research presented in the preprint? Yes It described the need, importance and the reason for the study.
    Are the methods well-suited for this research? Highly appropriate The methods were well detailed
    Are the conclusions supported by the data? Somewhat supported
    Are the data presentations, including visualizations, well-suited to represent the data? Highly inappropriate or unclear There was no data presentation as visuals, etc. in the article, except it was kept in another place
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly
    Is the preprint likely to advance academic knowledge? Highly likely It is an area that, if advanced, will help in healthcare promotion.
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, but it needs to be improved Data should be presented using various visual aids. It should provide more detailed explanations to enable scholars from different fields to learn easily.
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes Results and discussion

    Competing interests

    The authors declare that they have no competing interests.

  3. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/14017981.

    Summary of Main Findings.

    This study reveals shared transcriptomic signatures between Alzheimer's disease and epilepsy, highlighting synaptic pruning as a potential molecular connection between the two disorders. Through detailed transcriptomic analysis, the researchers discovered that dysregulated genes related to synaptic pruning may play a role in the pathological processes of both diseases. This research offers new insights into the common mechanisms underlying neurodegeneration and neurological disorders, proposing synaptic pruning as a viable therapeutic target for both Alzheimer's and epilepsy. By linking these two conditions, the study paves the way for innovative dual-targeting therapeutic strategies that could alleviate symptoms or slow disease progression in patients with either or both conditions.

    Major Issues

    Causal Mechanisms Not Established: The study indicates associations between synaptic pruning and disease but lacks experimental validation to confirm causation. Additional mechanistic studies are necessary to determine whether changes in synaptic pruning are truly causal factors.

    Sample Size and Diversity: If the research was based on small or homogeneous sample populations, the findings may not be applicable to broader populations, particularly considering genetic and environmental variations among Alzheimer's and epilepsy patients.

    Limited Functional Validation: Although transcriptomic data show gene dysregulation, more functional experiments (e.g., in vivo or in vitro studies) are needed to elucidate the roles of these genes in synaptic pruning and disease pathology.

    Minor Issues

    Terminology Clarification: Simplifying complex terminology or providing a glossary could enhance accessibility for readers unfamiliar with specialized fields.

    Graphical Representations: Improved figures or diagrams depicting shared pathways between Alzheimer's and epilepsy could enhance understanding.

    Flow and Structure: Reorganizing sections to emphasize key findings before delving into detailed transcriptomic data could better guide readers through the research narrative.

    Competing interests

    The author declares that they have no competing interests.

  4. Version published to 10.1101/2024.10.28.618752 on bioRxiv