1. Deborah Jiang Kristy S. Hwang Yvette Bordelon Liana G. Apostolova
Cortical Atrophy and Gene Expression in Parkinson’s Disease with Mild Cognitive Impairment
American Geriatrics Society 2013 Annual Scientific Meeting
Deborah Jiang Kristy S. Hwang Yvette Bordelon Liana G. Apostolova

2. Disclosures This research was funded by the
Medical Student Training in Aging Research Program (MSTAR)
National Institute on Aging (T35AG026736, R01 AG040770, P50 AG16570)
John A. Hartford Foundation
MetLife Foundation
Lillian R. Gleitsman Foundation
Lincy Foundation
Easton Consortium for Alzheimer’s Drug Discovery and Biomarker Development

3. Parkinson’s Disease One million cases US Four million worldwide
Increasing incidence with age
Majority idiopathic
Familial cases, disease-associated genes
Clinical scales vs. biomarkers

4. Parkinson’s Disease Neurodegenerative disease Substantia nigra
Lewy bodies with alpha-synuclein accumulation
Motor symptoms
Cognitive decline common non-motor change

5. Background
6-fold increased risk for developing dementia (PDD) relative to elderly controls
Significant gray matter atrophy found in PDD
Mild cognitive impairment (PDMCI) as transition stage

6. Objective
To compare cortical atrophy in PDCN (PD cognitively normal) and PDMCI groups
Exploratory analysis of association of peripheral blood gene expression with cortical atrophy

7. Study Design Longitudinal project Final enrollment 40
Currently enrolled 22
Preliminary analysis
Diagnosis of Parkinson’s Disease
CN OR MCI defined by Petersen criteria
No evidence of general medical condition that may influence cognitive performance

8. Image Processing
Coronal Fl3D T1 MPRAGE: TR 28, TE 4.5, FOV 22 cm, matrix 256x192, slice/gap 1.5/0 mm
Linear registration and scaling of the individual MRI scans to the ICBM 53 template using a 9 parameter linear transformation
Image nonuniformity correction using regularized tricubic B spline approach

9. Cortical Image Processing
Alignment to ICBM53 space
Skullstripping

10. Cortical Image Processing
3D hemispheric reconstruction and sulci tracing
Cortical flattening, sulcal averaging, cortical warping

11. Cortical Image Processing
3D parametric mesh hemispheric model
Mapping cortical thickness values to 3D mesh models

12. Gene Expression Peripheral blood RNA extracted with Paxgene tubes
Amplified, labeled, and hybridized onto Illumina Human RefSeq-8 BeadChip arrays, querying the expression of ~22,000 RefSeq curated transcripts followed by quality control, and quantile normalization with R and Bioconductor packages
29 selected genes

13. Statistical Analysis Used linear regression to investigate in 3D
Cortical thickness between PDCN and PDMCI groups
Association between cortical thickness and peripheral blood gene expression levels
Further correction for multiple comparison was done with permutation testing at a threshold of p<0.01

14. Demographics Data Variable (SD) PDCN n=5 PDMCI N=17
p-value, chi2, ANOVA
Age, yr
75.4 (6.6)
71.5 (8.6)
0.37
Gender, M:F
2:3
11:6
0.44
Education, yr
17.4 (0.9)
16.6 (2.4)
0.32
MMSE
27.4 (3.4)
27.4 (2.5)
0.99

15. Results

16. Results Significant Not significant
Atrophy of left entorhinal cortex in PDMCI
Memory-related PDMCI symptoms
Not significant
PDMCI atrophy in occipital lobes bilaterally
Right frontal area
Match deficits in visual processing and executive functions

17. Results

18. Summary
FOXL1 mRNA levels correlated with GREATER cortical thickness (p=0.021 R)
Transcription factor
Role in regulating Wnt/β-catenin pathway
OXER1 levels correlated with DECREASED cortical thickness (p= L, p= R)
Oxoeicosanoid receptor
Role in inflammatory signaling pathways

19. Future Rerun statistical analysis as enrollment continues
Once enrollment completed, look at longitudinal changes in cortical atrophy and gene expression
Include additional genes to current 29

20. Acknowledgements Dr. Liana Apostolova Kristy Hwang
MSTAR program at UCLA
Mary S. Easton Center for Alzheimer’s Disease Research

21. Deborah Jiang jiangdh@mail.uc.edu
Contact
Deborah Jiang