Evidence mapPaperPMID 41729360Full record

ArticleMolecular neurobiology2026

Regulon Reconstruction Uncovers Novel Deregulated Factors in Alzheimer's Disease.

Marcella Vitória Belém-Souza, Gustavo Barra-Matos, Gilderlanio Santana de Araújo

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Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Marcella Vitória Belém-SouzaGraduate Program in Genetics and Molecular Biology, Institute of Biological Sciences, Federal University of Pará, Belém, 66075-100, Brazil.
Gustavo Barra-MatosGraduate Program in Genetics and Molecular Biology, Institute of Biological Sciences, Federal University of Pará, Belém, 66075-100, Brazil.
Gilderlanio Santana de AraújoGraduate Program in Genetics and Molecular Biology, Institute of Biological Sciences, Federal University of Pará, Belém, 66075-100, Brazil. gilderlanio@ufpa.br.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative age-related disorder characterized by widespread transcriptional deregulation across multiple brain regions. Among the molecular players involved, the transcription factors (TFs) can regulate the expression of AD-related peptides (β-amyloid and tau). We aim to unveil reconstructed TF-centered networks and their dynamics across multiple brain regions. In this study, we conducted an exhaustive differential gene expression analysis, reconstructed TF-TF-centered regulatory networks, and performed master-regulation analyses across multiple regions. We used bulk RNA-seq data from 2,229 post-mortem samples from the ROSMAP, MAYO, and MSBB cohorts. To place these regulatory programs in a disease-relevant context, we integrated protein-protein interaction (PPI) data, experimental TF-target data, and AD-associated genetic risk loci as a translational layer. We assessed TF-centered regulons for 1,605 TFs and identified 354 master-regulators (MR-TFs) across multiple brain regions, including the parahippocampal gyrus, temporal cortex, and cerebellum, which exhibited the highest numbers of regulons. Overall, regulons fell within a moderate size range (median 55 targets), rather than into extensive large networks. Novel MR-TFs, including ADCYAP1, TEAD2, BCL6, MAFF, NFKBIA, were consistently identified as MR-TFs across tissues in AD. Furthermore, GUCY1B1, RBFOX2, and MEF2C were found conserved in the parahippocampal gyrus, inferior frontal gyrus, and posterior cingulate cortex. Additionally, our work identified the well-known AD-related genes BIN1, EGFR, and SPI1 as MR-TFs, reinforcing their functional roles as susceptibility risk markers in AD. This work established an MR-TF-centered integrated regulatory network map of AD, revealing MR-TFs as factors that orchestrate gene deregulation in a region- and cell-context-dependent approach, and providing a robust foundation for mechanistic and translational investigations in neurodegeneration.

Indexed as

Alzheimer DiseaseRegulonTranscription FactorsBrainGene Expression RegulationGene Regulatory NetworksHumansProtein Interaction MapsTranscription FactorsAlzheimer's diseaseRegulatory Transcriptional NetworkTranscriptional Factors

Identifiers

PMID41729360
PMCPMC12929348

What Socratic holds

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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 Socratic graph.