PreprintCC BYmedRxiv26 Oct 2026

Strategies to establish a biologically defined Parkinson's disease cohort prior to the onset of clinically significant motor symptoms

E. G. Brown¹
H. Blumenau
D.-E. Lafontant
A. R. Nair
N. Johnson
R. N. Alcalay
L. M. Chahine
C. S. Coffey
R. D. Dobkin
T. Foroud
D. Galasko
K. Merchant

9 more authors

B. Mollenhauer
K. L. Poston
A. Siderowf
C. M. Tanner
D. Weintraub
K. Marek
T. Simuni
T. F. Tropea
Parkinson's Precision Medicine Initiative

¹Department of Neurology, University of California San Francisco, San Francisco, CA, USA

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.

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BibTeX RIS

BibTeX

@misc{brown2026strategies,
  title = {{Strategies to establish a biologically defined Parkinson's disease cohort prior to the onset of clinically significant motor symptoms}},
  author = {E. G. Brown and H. Blumenau and D.-E. Lafontant and A. R. Nair and N. Johnson and R. N. Alcalay and L. M. Chahine and C. S. Coffey and R. D. Dobkin and T. Foroud and D. Galasko and K. Merchant and B. Mollenhauer and K. L. Poston and A. Siderowf and C. M. Tanner and D. Weintraub and K. Marek and T. Simuni and T. F. Tropea and Parkinson's Precision Medicine Initiative},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.26.26366535},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Strategies to establish a biologically defined Parkinson's disease cohort prior to the onset of clinically significant motor symptoms
AU  - E. G. Brown
AU  - H. Blumenau
AU  - D.-E. Lafontant
AU  - A. R. Nair
AU  - N. Johnson
AU  - R. N. Alcalay
AU  - L. M. Chahine
AU  - C. S. Coffey
AU  - R. D. Dobkin
AU  - T. Foroud
AU  - D. Galasko
AU  - K. Merchant
AU  - B. Mollenhauer
AU  - K. L. Poston
AU  - A. Siderowf
AU  - C. M. Tanner
AU  - D. Weintraub
AU  - K. Marek
AU  - T. Simuni
AU  - T. F. Tropea
AU  - Parkinson's Precision Medicine Initiative
PY  - 2026
DA  - 2026/10/26
PB  - medRxiv
DO  - 10.64898/2026.10.26.26366535
UR  - https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1
AB  - 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.
ER  -

Abstract

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