1. THE PARKINSON’S PROGRESSION MARKERS INITIATIVE
Biospecimen Analyses
Samantha Hutten

2. Received biospecimen requests
CSF
14%
DNA
25%
RNA
Serum 7%
Whole blood
Cell lines
Multiple 4%
Plasma4%
CSF
DNA
Plasma
RNA
Serum
Whole blood
Cell lines
Multiple
The PPMI Biospecimen Review Committee has received 144 biospecimen requests to date. Requests for PPMI samples have been diversified analyses across multiple matrices.

3. Approved biospecimen requests
CSF
Plasma
Serum
Cell lines
Whole blood
RNA
Multiple
The PPMI Biospecimen Review Committee has approved 28 biospecimen requests. 10 projects using PPMI samples are currently ongoing.

4. PPMI Genetics Core Analyses
Analysis
Matrix
Cohort(s)
Visit(s)
Project Details
Data Availability
NeuroX genotyping
DNA from whole blood
PD, HC, SWEDD, Prodromal, Genetic BL
PI: Andrew Singleton, PhD, National Institute on Aging
Title: Selected Genetic Variants Genotyped Using NeuroX Array
Currently available
GBA sequencing
PD, HC, & SWEDD
Title: GBA Sequencing
Data return timeline TBD
Immunochip genotyping
Title: Immunochip Genotyping on DNA Samples from PPMI
Whole exome sequencing
Title: Exome Sequencing of PPMI samples
Whole genome sequencing
All cohorts
Title: Whole Genome Sequencing and Analysis of PPMI Prodromal and Genetic Cohorts and Genetic Registry
APOE4 Genotyping
Title: APOE4 Genotyping
mRNA/miRNA sequencing
RNA from whole blood
BL,12, 24, 36 mo
PI: Kendall van Keuren-Jensen, PhD, TGen Foundation
Title: RNAseq Pilot Study
PD & HC (BL, 12, 24, 36 mo) & LRRK2 BL: (expected May/June)
DNA methylation
Whole blood
PI: Dena Hernandez, PhD, National Institute on Aging
Title: DNA Methylation in PPMI

5. PPMI biologics Core Analyses
Analyte/Platform
Matrix
Cohort(s)
Visit(s)
Project Details
Data Availability
CSF total aSyn and Hb (Covance/
BioLegend immunoassay)
CSF
All cohorts
All available visits
PI: Peggy Taylor, PhD, BioLegend
Title: Alpha-synuclein and Hb: Pilot Study
Currently available
CSF Aβ, tau, and p-tau181
(Innogenetics INNO-BIA AlzBio3 immunoassay & Roche Elecsys automated immunoassay
PI: Les Shaw, PhD, University of Pennsylvania
Title: A-beta 1-42, t-tau and p-tau 181 Measurements in 120 PPMI CSF Samples using xMAP/Luminex Multiplex Immunoassay: Pilot Study
GCase activity and Glycosphingolipids
Whole blood, CSF, & plasma
PD, HC, & SWEDD
BL V04 (12 mo), V06 (24 mo), & V08 (36 mo)
PI: Pablo Sardi, PhD, Sanofi
Title: GBA-Related Biomarkers in Parkinson’s disease
Expected July (plasma lipids) & October 2018 (WB activity), CSF TBD

6. Brc Biospecimen Approvals
Analyte
Matrix
Cohort(s)
Visit(s)
Project Details
Data Availability
αSyn transcripts
RNA from whole blood
PD & HC BL
PI: Clemens Scherzer, MD, Harvard University
Title: Evaluation of PD-linked Transcripts in PPMI
Currently available
ApoA1 and EGF
Plasma
BL, V02 (6 mo), & V04 (12 mo)
PI: Alice Chen-Plotkin, MD, MSc, University of Pennsylvania
Title: Plasma Apolipoprotein A1 Level as a Biomarker in Parkinson's disease
IGF-1
Serum
PI: Maria Teresa Pellecchia, PhD, University of Salerno
Title: Insulin-like Growth Factor-1 as a Biomarker of Early Cognitive Impairment in Parkinson’s disease
mRNA transcripts
PI: Judith Potashkin, PhD, Rosalind and Franklin University
Title: Whole Blood RNA Biomarkers of PD
Currently available
SNCA genotyping
DNA from whole blood
PI: Matthew Farrer, PhD, University of British Columbia
Title: Clinical, Imaging, and Plasma and CSF Correlates of Alpha-synuclein Genomic Variability
PD, HC, & SWEDD
BL, V04 (12 mo), V06 (24 mo), &
V08 (36 mo)
PI: Martin Rabey, BioShai Ltd.
Title: Validation of a Blood-based Gene Expression Assay for Early Diagnosis and Monitoring Disease

7. Brc Biospecimen Approvals
Analyte
Matrix
Cohort(s)
Visit(s)
Project Details
Data Availability
PD2 peptoid
Serum
PD & HC BL
PI: Dwight German, PhD, UT Southwestern
Title: Blood Biomarker for PD
Currently available
Cell-free mitochondrial DNA
CSF
BL & V08 (36 mo)
PI: Gavin Hudson, PhD, Newcastle University
Title: The role of cell-free mitochondrial DNA in neurodegenerative disease
Catecholamines
BL, V04 (12 mo), & V06 (24 mo)
PI: Thomas Kremer, PhD, F. Hoffman-la Roche, Ltd.
Title: CSF neurotransmitter metabolites as promising diagnostic and disease severity biomarkers in early-stage Parkinson’s disease patients
Expected mid-May)

8. Brc Cell Lines Approvals
Analyte/Pathway
Matrix
Cohort(s)
Project Details
Data Availability
PINK1
Fibroblasts
PD & HC
PI: Satpal Virdee, PhD, University of Dundee
Title: Profiling PINK1-Parkin Functionality in Patient Fibroblasts Using Chemical Probes
Expected June
Miro
PI: Xinnan Wang, PhD, Stanford University
Title: Miro, a Biomarker for Parkinson’s disease
Data return timeline TBD
ER stress
Fibroblasts and iPSCs
PD, HC, & Genetic Cohort
PI: Charleen Chu, MD, PhD, University of Pittsburgh
Title: ER Stress and Mitochondrial Homeostasis in Parkinson’s disease
Calcium activity
PI: Nilima Prakash, PhD, Hamm-Lippstadt University of Applied Sciences
Title: Altered calcium activity patterns in developing dopaminergic neurons from PD patients as an early indicator of disease predisposition or progression
Urate and Nrf2
iPSCs
PI: Rachit Bakshi, PhD, Massachusetts General Hospital/MIND
Title: Urate and Nrf2 pathway effects on mutant LRRK2 toxicity in iPSC-derived DA neurons

9. GCase substrate lipids
Comprehensive data generation of the original cohort
DNA
WGS
WES
Methylation
(Baseline)
Genotyping
SNP Array
RNA
(Whole Blood)
mRNAseq
miRNAseq
CSF
Total α-synuclein
Aβ1-42, tau, p-tau
mtDNA copy number
GCase substrate lipids
Whole Blood
GCase activity
Plasma
Investigating genetic and biological indices across compartments within the same individuals to comprehensively profile the PPMI original cohort