ArticleJournal of Alzheimer's disease reports
Exploratory epilepsy-derived transcriptomic projection reveals region-sensitive molecular remodeling in Alzheimer's disease.
Article in Journal of Alzheimer's disease reports. 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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5 authors.
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Abstract
Background: Alzheimer's disease (AD) is frequently accompanied by seizures or subclinical epileptiform activity, but the transcriptomic context linking AD-related neurodegeneration with epilepsy-related network dysfunction remains unclear. Objective: To apply an exploratory epilepsy-derived directional transcriptomic projection framework to examine region-sensitive molecular organization in AD brain tissues. Methods: A directional reference was generated from GSE268714 by defining seizure onset zone (SOZ)-upregulated and SOZ-downregulated genes from an unpaired exploratory SOZ-versus-non-involved zone (NIZ) contrast, because patient-level identifiers were not recoverable. This reference was projected onto AD cohorts GSE5281, GSE132903, and GSE48350. EpilepsyScore was calculated as ssGSEA_Up minus ssGSEA_Down. In GSE5281, primary inference was restricted to region-stratified analyses. Results: Region-stratified analyses showed lower EpilepsyScore values across several AD-relevant regions, with the clearest separation in the middle temporal gyrus (MTG). Within MTG, continuous module-level associations with synaptic and glia-associated programs were directionally consistent but not statistically significant. Median-based grouping was used only for exploratory visualization and pathway-level contrast. External cohorts showed directionally concordant but context-dependent support. Matched random-signature benchmarks were not significant, indicating that EpilepsyScore should not be interpreted as an epilepsy-specific molecular signature. Conclusions: This study provides a hypothesis-generating cross-disease projection framework for exploring region-sensitive transcriptomic organization in AD. Future cell-type, spatial, and mechanistic evaluation is required.
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