RNA-Seq analysis of the parietal cortex in Alzheimer's disease reveals alternatively spliced isoforms related to lipid metabolism

James D. Mills, Thomas Nalpathamkalam, Heidi I. L. Jacobs, Caroline Janitz, Daniele Merico, Pingzhao Hu, Michael Janitz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Web of Science)

Abstract

The parietal cortex of the human brain plays a unique role in the coordination of movement and in the integration of signals from the other cortices. Because of its extensive connections and involvement in many higher-order cognitive functions, neurodegenerative changes in the parietal lobe are believed to be crucial in the early symptoms of Alzheimer's disease (AD). Little is known about the transcriptome of this part of the human brain or how it is perturbed by the neurodegenerative process. To that end, we performed mRNA sequencing using the Illumina RNA-Seq technique on samples derived from normal and AD parietal lobes. Gene expression analysis evaluating alternatively spliced isoform expression and promoter usage revealed surprisingly elevated transcriptome activity in the AD condition. This phenomenon was particularly apparent in the alternative usage of transcriptional start sites. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways related to lipid metabolism, thus highlighting the importance of astrocyte activity in the neurodegenerative process. We also identified an upregulation of the diazepam-binding inhibitor (DBI) gene in AD, as the result of a splicing switch toward shorter, intron-retaining isoforms driven by alternative promoters and was coupled with a simultaneous decrease in the abundance of protein-coding transcripts. These two DBI isoforms have not been described previously.
Original languageEnglish
Pages (from-to)90-95
JournalNeuroscience Letters
Volume536
DOIs
Publication statusPublished - 1 Mar 2013

Keywords

  • Neurodegeneration
  • Human brain
  • Next-generation sequencing
  • Transcriptome
  • Diazepam-binding inhibitor

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