Brain Transcriptome Profiling in Alzheimer’s Disease Using RNA-Seq

Alzheimer's disease (AD) is a neurodegenerative disorder that results from a loss of synaptic transmission and ultimately cell death. The cellular pathology of AD includes neuritic plaques composed of beta-amyloid peptide (Abeta) and neurofibrillary tangles composed of hyperphosphorylated tau, with neuronal loss in specific brain regions. However, the mechanisms that induce neuronal cell loss remain elusive.

Current research provides numerous hints concerning molecular mechanisms of the AD pathogenesis. It is however necessary to obtain a global view, on the scale of the whole genome, of the molecular processes leading to neuronal pathology in AD. The goal of this project is to establish a molecular map of the brain transcriptome in Alzheimer’s disease in order identify markers of the neurodegenerative process such as alternatively spliced mRNA isoforms or genes with elevated or suppressed expression. Due to its global character this project should gain new insights not only into the pathogenesis of the AD but also physiology of the human brain.

The project involves application of Illumina next-generation DNA sequencing technology for the whole transcriptome profiling and identification of alternatively spliced mRNA variants. Moreover, for downstream evaluation of candidate genes, RT-PCR, RNA interference, DNA transfection into human cell lines and site-directed mutagenesis are applied.

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