Objective: PPMI is a longitudinal, observational study investigating clinical, imaging, genetic and biofluid biomarkers to accelerate therapeutic development for Parkinson’s disease (PD) and related synucleinopathies from start of neurodegeneration through clinical PD.

Background: PPMI is a broad longitudinal, global study, sponsored by the Michael J Fox Foundation. All PPMI data is open source, available for researchers worldwide (www.ppmi-info.org). PPMI includes enrollment and follow-up of densely phenotyped populations (n=4000) at 50 sites. Participants include a PD newly diagnosed untreated cohort, a prodromal cohort focused on RBD and hyposmia and healthy controls. PPMI also has enrolled >100,000 participants in remote assessment strategies under the umbrella of myPPMI, a web portal that provides opportunities for acquisition of data and return of personalized data to study participants.

Method: PPMI data validated the α-synuclein seed amplification assay (asyn SAA) in CSF. These data coupled with dopamine transporter imaging results have led to a biomarker driven definition for PD and the introduction of the concept of Neuronal Synuclein disease (NSD) encompassing PD, dementia with Lewy Bodies, and RBD and a staging platform, NSD-ISS. Based on these data PPMI has developed a novel sequential screening paradigm of olfactory function followed by CSF for asyn SAA status to examine the earliest stage of degeneration. Goal is to enroll 1000 CSF SAA positive prodromal participants.

Results: PPMI has enrolled >1000 PD participants and 2500 prodromal participants with biomarker data enabling participants to be staged by the NSD-ISS. PPMI has initiated enrollment with olfaction followed by CSF. Early data demonstrates that 65% of participants screened with severe hyposmia are asynSAA positive. Recognizing that many NSD participants are likely to have additional biomarkers of neurodegeneration, PPMI is acquiring a wide array of plasma and CSF biomarkers including ptau217, ptau243, NfL, GFAP, multiplex Nulisa and Olink in the PPMI NSD cohorts.  PPMI DAT imaging data has been further optimized utilizing MIAKAT, an advanced analysis pipeline.

Conclusion: PPMI continues to longitudinally follow existing participants and to enroll a new NSD defined cohort based on asynSAA status. Participants will be further characterized by an extensive fluid biomarker and imaging biomarker signature.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-progression-markers-initiative-ppmi-a-biomarker-engine-for-therapeutic-development-for-pd-and-related-synucleinopathies/