Evidence map›Paper›PMID 40670811›Full record

ArticleJournal of molecular neuroscience : MN2025

Multi-tissue Methylation Analysis of Alzheimer's Disease: Insights into Pathways, Modules, and Key Genes.

Tianshu Zhu, Yue Wang, Han Wang, Zheyu Xu, Peng-Fei Zhang, Zhiming Lu

Abstract read
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Article in Journal of molecular neuroscience : MN, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Tianshu ZhuDepartment of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China.
Yue WangDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Han WangMedical Neurobiology Lab, Inner Mongolia Medical University, Huhhot, 010110, China.
Zheyu XuShandong Second Medical University, Weifang, 261053, China.
Peng-Fei ZhangDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. 2019020844@qdu.edu.cn.
Zhiming LuDepartment of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, China. luzhiming@sdu.edu.cn.

Funding

National Natural Science Foundation of China 82272414
6 · The paper itself

Abstract

DNA methylation plays a crucial role in the onset and progression of Alzheimer's disease (AD). Genome-wide methylation analysis of multi-tissue data can provide insights into the pathology and diagnostic biomarkers of AD. Computational tools were employed to identify pathways associated with AD and to develop a poly-methylation score (PMS). Key genes within the identified pathways were determined through module analysis and protein-protein interaction networks followed by validation in β-amyloid 42-induced cellular models. Linear mixed-effects model was used to investigate the longitudinal relationship between PMS and changes in AD phenotypes. AD-related pathways exhibited tissue specificity. The key genes in blood, frontal cortex, neurons, and glial cells were THBS1, TGFB1, HIF1A, and KLF4, respectively. Furthermore, the expression alterations of these genes were validated in three cellular models (SH-SY5Y, HMC3, and THP-1). Notably, higher PMS was significantly correlated with accelerated declines in cerebral metabolic rate and cognitive function. Using machine learning to analyze methylation data and identify key genes in AD patients enhanced our understanding of AD pathogenesis. Further research is needed to validate the potential of these key genes as intervention targets for AD.

Indexed as

Alzheimer DiseaseDNA MethylationAgedCell Line, TumorFemaleGene Regulatory NetworksHumansHypoxia-Inducible Factor 1, alpha SubunitKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleNeurogliaNeuronsProtein Interaction MapsThrombospondin 1Transforming Growth Factor beta1HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitKLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription FactorsThrombospondin 1Transforming Growth Factor beta1Alzheimer’s diseaseBiological mechanismMachine learningMethylationPoly-methylation score

Identifiers

PMID40670811

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.