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In this review, we describe lessons learned from prior enrollment and current strategies for PPMI eligibility. Severe hyposmia remains the strongest clinical predictor of aggregated synuclein as measured by a positive cerebrospinal fluid alpha\u2010synuclein seed amplification assay (CSF aSyn SAA). CSF aSyn SAA is positive before dopamine transporter binding decreases, as measured by dopamine imaging. PPMI's adaptive eligibility criteria have enabled efficient identification of people in the early stage of neuronal synuclein disease defined by biomarkers alone and can inform future therapeutic studies. 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