Strategies to establish a biologically defined Parkinson’s disease cohort prior to the onset of clinically significant motor symptoms
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Identifying individuals at risk for neurodegeneration is a priority for clinical trials. Parkinson’s Precision Medicine Initiative (PPMI) deploys strategies to enroll individuals before typical clinical Parkinson’s disease symptoms: recruiting polysomnogram-confirmed REM sleep behavior disorder (RBD) and central identification of hyposmia via smell testing. Groups were divided into RBD with and without hyposmia (RBD+Hyposmia, RBD-Hyposmia) and hyposmia with and without self-reported dream enactment behavior (Hyposmia+DEB, Hyposmia-DEB). Participants underwent clinical and biomarker testing including CSF alpha-synuclein seed amplification assay (CSFaSynSAA) and dopamine transporter imaging. While all enrollment strategies showed robust enrichment for CSFaSynSAA positivity, RBD+Hyposmia and Hyposmia+DEB were more likely CSFaSynSAA+ (94% and 85%) vs RBD-Hyposmia (40%) and Hyposmia-DEB (55%). Among CSFaSynSAA+, RBD+Hyposmia and Hyposmia+DEB had more mood, autonomic, and cognitive symptoms than Hyposmia-DEB. PPMI identified a large biologically-defined early neuronal synucleinopathy cohort and demonstrated biomarker and multi-domain clinical heterogeneity within CSFaSynSAA+ individuals prior to symptom onset.
Source: medRxiv
Authors: Ethan G. Brown, Helena Blumenau, David-Erick Lafontant, Anuprita R. Nair, Noah Johnson, Roy N. Alcalay, Lana M. Chahine, Christopher S. Coffey, Roseanne D. Dobkin, Tatiana Foroud, Douglas Galasko, Kalpana Merchant, Brit Mollenhauer, Kathleen L. Poston, Andrew Siderowf, Caroline M. Tanner, Daniel Weintraub, Kenneth Marek, Tanya Simuni, Thomas F. Tropea
Institutions: University of California, San Francisco, University of Iowa, Columbia University Irving Medical Center, Tel Aviv Sourasky Medical Center, Rutgers, The State University of New Jersey, Indiana University Indianapolis, Indiana University School of Medicine, University of California San Diego, Northwestern University, Universitätsmedizin Göttingen, Paracelsus Elena Klinik Kassel, Stanford Medicine, Stanford University, University of Pennsylvania, Institute for Neurodegenerative Disorders
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7224086409