Skin α-Synuclein Seeding Activity in Patients with Type 1 Gaucher Disease.

Background: Patients with type 1 Gaucher disease (GD1) have a significantly increased risk of developing Parkinson's disease (PD).

Objective: The objective of this study was to evaluate skin α-synuclein (αSyn) seeding activity as a biomarker for GD1-related PD (GD1-PD).

Methods: This single-center study administered motor and cognitive examinations and questionnaires of nonmotor symptoms to adult patients with GD1. Optional skin biopsy was performed for skin αSyn seed amplification assay (αSyn SAA) using real-time quaking-induced conversion assay.

Results: Forty-nine patients were enrolled, and 36 underwent skin biopsy. Two study participants had PD. Ten participants were αSyn SAA positive (27.8%), 7 (19.4%) were intermediate, and 19 (52.8%) were negative. Positive αSyn seeding activity was observed in the single GD1-PD case who consented to biopsy. αSyn SAA positivity was associated with older age (p = 0.043), although αSyn SAA positivity was more prevalent in patients with GD1 than historic controls.

Conclusions: Longitudinal follow-up is required to determine whether skin αSyn seeding activity can be an early biomarker for GD1-PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.