Objective: To utilize a centralized screening paradigm for early stage NSD based on sequential olfactory dysfunction (measured by University of Pennsylvania Smell Identification test (UPSIT)) followed by the CSF alpha synuclein seed amplification assay (asyn SAA)

Background: The Parkinson’s Progression Markers Initiative (PPMI) is a longitudinal, international, observational study designed to investigate disease progression biomarkers for Parkinson’s and related synucleinopathies. A major focus of PPMI has been to enroll study participants at the earlier stages of neurodegeneration based on a synuclein biomarker signature.  PPMI has now developed a screening paradigm that takes advantage of the very robust association between olfactory dysfunction and the presence of synuclein.

Method: PPMI has deployed a widespread online screening tool, Smell Test Direct (ST Direct), that has screened >100,000 study participants for olfactory dysfunction. The PPMI central screening team at Indiana University (IU) contacts hyposmic participants from ST Direct to discuss further participation in PPMI, including travel to PPMI sites for a lumbar puncture to assess asyn SAA. PPMI sites consent participants and acquire CSF. Participants found to be asyn SAA positive are invited to enroll in the clinical PPMI study. Participants found to be asyn SAA negative are invited to participate in myPPMI (an online portal). Extensive participant resources, education, and communication are provided throughout the screening process.

Results: To date, 1297 hyposmic candidates were offered SAA testing, and 518 were accepted—approximately 40%. 144 individuals have completed an LP, while others are scheduled to undergo LP screening. SAA results are available for 100 participants, and 65 were asyn SAAA positive. The goal is to enroll 1000 participants.

Conclusion: PPMI has successfully developed a centralized screening paradigm for early-stage NSD using UPSIT as an easily accessible, relatively inexpensive initial screen followed by LP to acquire CSF for the asyn SAA assay.  Early data demonstrates that approximately 40% of hyposmic participants agree to subsequent LP and that 65% of the LPs are asyn SAA positive. This provides a clear proof of concept for the PPMI screening strategy. The study will continue to enhance screening opportunities and education to further optimize the olfaction/CSF screening paradigm.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/screening-for-neuronal-synuclein-disease-nsd-using-cerebrospinal-fluid-csf-in-the-parkinson-progression-marker-initiative-ppmi/