RNA-Seq to deliver a quantum leap forward in understanding Alzheimer’s disease

The prevalence of Alzheimer’s disease (AD) is increasing rapidly in the Western world and is poised to have a significant economic and societal impact. Current treatments do not alter the underlying disease processes meaning new treatments are required if this imminent epidemic is to be averted. The clinical manifestations of AD are secondary to a substantial loss of cortical neurons.

Effective neuroprotective strategies will require the discovery of both preclinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. While the biomarkers and pathogenic mechanisms may overlap, it is likely that new approaches are required to identify novel elements of the disease.

Transcriptomic analyses, that assume no a priori etiological hypotheses, promise much in elucidating the pathogenesis of complex diseases like AD. RNA-Seq is not only highly suited to investigations of the genomically complex human brain tissue but it can potentially overcome technical issues inherent to case-control comparisons of postmortem brain tissue in neurodegenerative diseases. Moreover, RNA-Seq goes beyond the detection of transcripts that correspond to an existing genomic sequence. With this technique, the exact location of transcription boundaries can be identified with single base resolution. These features make RNA-Seq particularly useful for studying complex transcriptomes, such as those found in the human brain.

Sutherland GT, Janitz M, Kril JJ. (2010) RNA-Seq and the pathogenesis of Alzheimer’s disease.  Journal of Neurochemistry [Epub ahead of print]. [article]