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.
GLOSSARY
- ATXN2=
- ataxin-2;
- CAM=
- cell adhesion molecule;
- CON=
- controls;
- CRH=
- corticotropin-releasing hormone;
- CSF3=
- granulocyte colony-stimulating factor;
- DE=
- differential gene expression;
- DLB=
- dementia with Lewy bodies;
- dPSI=
- delta PSI;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- DST=
- dystonin;
- fc=
- fold change;
- GO=
- gene ontology;
- HSPH1=
- heat shock protein 105 kDa;
- KRT5=
- keratin 5;
- LRRFIP1=
- leucine-rich repeat flightless-interacting protein 1;
- NF-κB=
- nuclear factor κB;
- OPKM=
- observations per kilobase of transcript length per million aligned reads;
- PD=
- Parkinson disease;
- PD-D=
- Parkinson disease with dementia;
- PENK=
- proenkephalin;
- PSI=
- percent spliced in;
- qRT=
- quantitative real-time;
- RBCC=
- N-terminal RING finger/B-box/coiled coil;
- RELA=
- rel-like domain-containing;
- RNA-seq=
- RNA sequencing;
- RPKM=
- reads per kilobase of transcript length per million aligned reads;
- SELE=
- selectin-E;
- SRRM1=
- serine/arginine repetitive matrix 1;
- SST=
- somatostatin;
- TRIM=
- tripartite motif;
- TRIM9=
- tripartite motif 9;
- VGF=
- Vgf nerve growth factor
Footnotes
↵† Deceased.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/ng for full disclosure forms. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org/ng
- Received October 30, 2015.
- Accepted in final form March 21, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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