RNASeq AD vs Normal brain
Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease
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. Next-generation sequencing of the whole transcriptome (RNA-Seq) provides a powerful alternative to microarray-based methods, both in terms of quantitative and qualitative analysis of gene expression. In the present study we used Illumina RNA-Seq analysis 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. For the first time, this study provides transcriptome analysis from distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Furthermore, our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.