Next-generation profiling to identify the molecular etiology of Parkinson dementia.
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.
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Adrienne
A
Henderson-Smith
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Jason J
JJ
Corneveaux
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Matthew
M
De Both
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Lori
L
Cuyugan
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Winnie S
WS
Liang
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Matthew
M
Huentelman
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Charles
C
Adler
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Erika
E
Driver-Dunckley
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Thomas G
TG
Beach
Neurogenomics Division (A.H.-S., J.J.C., M.D.B., L.C., W.S.L., M.H., T.L.D.), Collaborative Sequencing Center (L.C., W.S.L.), Translational Genomics Research Institute, Phoenix; Division of Neurology (C.A., E.D.-D.), Mayo Clinic, Scottsdale; Banner Sun Health Research Institute (T.G.B.), Sun City, AZ.
Travis L
TL
Dunckley