Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease

Natalie A. Twine, Karolina Janitz, Marc R. Wilkins, Michal Janitz

Research output: Contribution to journalArticlepeer-review

242 Citations (Scopus)

Abstract

Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.
Original languageEnglish
Article numbere16266
Number of pages13
JournalPLoS One
Volume6
Issue number1
DOIs
Publication statusPublished - 2011

Open Access - Access Right Statement

©2011 Twine et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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