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Identification and Enrollment of Individuals Prior to Parkinson's Disease Diagnosis: Biomarker-Driven Adaptive Eligibility and Enrollment into the Parkinson's Progression Markers Initiative
Editorial   Open access

Identification and Enrollment of Individuals Prior to Parkinson's Disease Diagnosis: Biomarker-Driven Adaptive Eligibility and Enrollment into the Parkinson's Progression Markers Initiative

Ethan G Brown, Lana M Chahine, Roseanne D Dobkin, Tanya Simuni, Tatiana Foroud, Laura E A Heathers, Thomas F Tropea, Craig E Stanley Jr, Bridget A McMahon, Norbert Brüggemann, …
Annals of neurology
05/14/2026
DOI: 10.1002/ana.78246
PMID: 42132059
url
https://doi.org/10.1002/ana.78246View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

To better understand the earliest stages of alpha-synucleinopathy, the Parkinson's Progression Markers Initiative (PPMI) has enrolled participants prior to the diagnosis of Parkinson's disease (PD) or dementia with Lewy Bodies (DLB). 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-synuclein 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. ANN NEUROL 2026.

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