ArticleResearch square2026
Isoform Remodeling and Promoter Switching Identify Altered Transcriptional Regulation in Alzheimer's Disease Frontal Cortex.
Article in Research square, 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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Abstract
backgroundAlzheimer's disease (AD) is associated with transcriptional dysregulation, but gene-level analyses may overlook isoform changes. We investigated how differential isoform usage, promoter selection, and splicing contribute to transcriptome remodeling in the AD frontal cortex.
methodsWe analyzed Oxford Nanopore long-read RNA sequencing data from frontal cortex of six individuals with AD and six controls. Transcripts were quantified using Bambu, and differential isoform usage was assessed using IsoformSwitchAnalyzeR. Promoter usage and SUPPA2-derived percent-spliced-in values were tested using beta regression. Transcription factor motif enrichment was evaluated at differentially used promoters. Transcript-level effects were compared with an independent short-read cohort.
resultsWe identified 109 isoform-switching events involving 96 isoforms across 86 genes, including
conclusionsAD-associated transcriptome remodeling extends beyond gene-level abundance to include changes in isoform proportions, promoter selection, and transcript structure. These findings implicate transcription initiation and RNA processing as complementary layers of dysregulation in AD.
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