THE PARKINSON’S PROGRESSION MARKERS INITIATIVE Biospecimen Analyses Samantha Hutten

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.

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.

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

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

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

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)

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

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