Evidence map›Paper›PMID 40250147›Full record

ArticleEpilepsy & behavior : E&B2025

Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.

Abdallah M Eteleeb, Suélen Santos Alves, Stephanie Buss, Mouhsin Shafi, Daniel Press, Norberto Garcia-Cairasco, Bruno A Benitez

Abstract read
In one paragraph

Article in Epilepsy & behavior : E&B, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers 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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3 · Its place in the literature

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1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Abdallah M EteleebDepartment of Psychiatry, Washington University, Saint Louis, St. Louis, MO, United States of America; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University, St. Louis, MO, United States of America.
Suélen Santos AlvesDepartment of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil.
Stephanie BussDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
Mouhsin ShafiDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
Daniel PressDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America.
Norberto Garcia-CairascoDepartment of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Department of Physiology, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Brazil.
Bruno A BenitezDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. Electronic address: bbenitez@bidmc.harvard.edu.

Funding

Multi-tissue High-throughput Proteomic and Genomic Study in Parkinson's DiseaseR01NS118146 · NINDS · WASHINGTON UNIVERSITY · PI BENITEZ, BRUNO · 2020 to 2025
$3.2M
Identification and characterization of molecular subtypes of Alzheimer's disease associated with cognitive function through cross-omics data integrationK25AG083057 · NIA · WASHINGTON UNIVERSITY · PI Abdallah M Eteleeb · 2023 to 2026
$594k
The role of CSPalpha in Adult onset neuronal Lipofuscinosis pathogenesisR21NS127211 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BENITEZ, BRUNO A. · 2022 to 2022
$491k
NIA NIH HHS K25 AG083057NINDS NIH HHS R01 NS118146NINDS NIH HHS R21 NS127211
6 · The paper itself

Abstract

BACKGROUND &

objectiveAlzheimer's Disease (AD) patients at multiple stages of disease progression have a high prevalence of seizures. However, whether AD and epilepsy share pathophysiological changes remains poorly defined. In this study, we leveraged high-throughput transcriptomic data from sporadic AD cases at different stages of cognitive impairment across multiple independent cohorts and brain regions to examine the role of epilepsy-causing genes.

methodsEpilepsy-causing genes were manually curated, and their expression levels were analyzed across bulk transcriptomic data from three AD cohorts and three brain regions. RNA-seq data from sporadic AD and control cases from the Knight ADRC, MSBB, and ROSMAP cohorts were processed and analyzed under the same analytical pipeline. An integrative clustering approach employing machine learning and multi-omics data was employed to identify molecularly defined profiles with different cognitive scores.

resultsWe found several epilepsy-associated genes/pathways significantly dysregulated in a group of AD patients with more severe cognitive impairment. We observed 15 genes consistently downregulated across the three cohorts, including sodium and potassium channels genes, suggesting that these genes play fundamental roles in cognitive function or AD progression. Notably, we found 25 of these genes dysregulated in earlier stages of AD and become worse with AD progression.

conclusionOur findings revealed that epilepsy-causing genes showed changes in the early and late stages of AD progression, suggesting that they might be playing a role in AD progression. We can not establish directionality or cause-effect with our findings. However, changes in the epilepsy-causing genes might underlie the presence of seizures in AD patients, which might be present before or concurrently with the initial stages of AD.

Indexed as

Alzheimer DiseaseBrainEpilepsyTranscriptomeAgedAged, 80 and overCognitive DysfunctionCohort StudiesDisease ProgressionFemaleGene Expression ProfilingHumansMaleAlzheimer diseaseBrainEpilepsyMulti-omicsSynaptopathyTranscriptomics

Identifiers

PMID40250147
PMCPMC12163898

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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.