The α-Synuclein seeding assay discriminates between LRRK2 p.Gly2019Ser variant carriers with and without Parkinson's disease.

Background: Reliable biomarkers for Parkinson's disease (PD) pathology detection are essential for research. The alpha-synuclein (aSyn) seed amplification assay (SAA) is a validated biomarker for misfolded aSyn. Objectives: To assess the association between aSyn SAA and LRRK2-related PD (LRRK2-PD) and its link to mitochondrial genetic burden. Methods: We included N=76 LRRK2 p.Gly2019Ser variant carriers (N=22 affected, N=54 unaffected), N=714 patients with idiopathic PD (iPD), and N=411 controls from Norway. We analyzed cerebrospinal fluid (CSF)-based aSyn SAA in N=10 PD patients and N=30 unaffected LRRK2 p.Gly2019Ser carriers, alongside N=6 controls and N=56 iPD patients. A mitochondrial po