Next-generation profiling to identify the molecular etiology of Parkinson dementia

Adrienne Henderson-Smith, Jason J. Corneveaux, Matthew De Both, Lori Cuyugan, Winnie S. Liang, Matthew Huentelman, Charles Adler, Erika Driver-Dunckley, Thomas G. Beach, Travis L. Dunckley

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objective: We sought to determine the underlying cortical gene expression changes associated with Parkinson dementia using a next-generation RNA sequencing approach. Methods: In this study, we used RNA sequencing to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex from neurologically normal control patients, patients with Parkinson disease, and patients with Parkinson disease with dementia. Results: Genes overexpressed in both disease states were involved with an immune response, whereas shared underexpressed genes functioned in signal transduction or as components of the cytoskeleton. Alternative splicing analysis produced a pattern of immune and RNA-processing disturbances. Conclusions: Genes with the greatest degree of differential expression did not overlap with genes exhibiting significant alternative splicing activity. Such variation indicates the importance of broadening expression studies to include exon-level changes because there can be significant differential splicing activity with potential structural consequences, a subtlety that is not detected when examining differential gene expression alone, or is underrepresented with probe-limited array technology.

Original languageEnglish (US)
Article numbere75
JournalNeurology: Genetics
Volume2
Issue number3
DOIs
StatePublished - Jun 1 2016

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

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    Henderson-Smith, A., Corneveaux, J. J., De Both, M., Cuyugan, L., Liang, W. S., Huentelman, M., Adler, C., Driver-Dunckley, E., Beach, T. G., & Dunckley, T. L. (2016). Next-generation profiling to identify the molecular etiology of Parkinson dementia. Neurology: Genetics, 2(3), [e75]. https://doi.org/10.1212/NXG.0000000000000075