Movement disorders : official journal of the Movement Disorder Society
September 28, 2026 · via Europe PMC
α-Synuclein Seeding Discriminates Between LRRK2 G2019S Variant Carriers with and Without Parkinson's Disease.
Lüth T, Gabbert C, Kleinz T, +10 more, Global Parkinson's Genetics Program (GP2).
AI summary — for doctors, generated from the abstract only
CSF alpha-synuclein seed amplification distinguished LRRK2 G2019S carriers with Parkinson disease from unaffected carriers, and mitochondrial genetic burden related to seeding.
What was studied
A Norwegian study of LRRK2 G2019S carriers, iPD patients and controls with CSF SAA in a subset and mitochondrial polygenic scores, with PPMI replication.
Key findings
- Seeding in 80% of LRRK2-PD and 1 unaffected carrier (AUC 0.97)
- Higher mitochondrial polygenic score associated with seeding (OR 1.54)
- Associations with SAA kinetics in both cohorts
Clinical relevance
Supports SAA in LRRK2 research; small SAA subsets.
Who should care
Limitations
Small number of LRRK2-PD with SAA.
SAA discriminates LRRK2-PD and may relate to mitochondrial genetics.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Reliable biomarkers for Parkinson's disease (PD) pathology detection are essential for research. α-Synuclein (aSyn) seed amplification assay (SAA) is a validated biomarker for misfolded aSyn.
Objective
The aim was 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 polygenic score (MGS) was derived from genotyping data, using Parkinson's Progression Markers Initiative (PPMI) as an additional cohort (iPD: N = 355, LRRK2-PD: N = 118). In patients with PD, we explored the association between mitochondrial genetic burden and aSyn SAA outcome as well as SAA kinetic measurements.
Results
Seeding was observed in 80% of patients with LRRK2-PD and in 1 unaffected variant carrier (AUC = 0.97, confidence interval [CI] 0.92-1.00). In an exploratory meta-analysis across 2 PD cohorts, higher MGS was associated with increased aSyn seeding (pooled β = 0.43, odds ratio [OR] = 1.54, P = 0.014). In the Norwegian cohort, assessing aSyn SAA kinetic measurements, higher MGS was associated with a higher maximum slope (β = 1.22, standard error [SE] = 0.50, P = 0.020). In PPMI, higher MGS was associated with shorter time to threshold (β = -0.34, SE = 0.13, P = 0.007) and time to maximum slope (β = -0.35, SE = 0.13, P = 0.007).
Conclusions
CSF-based aSyn SAA can discriminate between LRRK2-PD and unaffected carriers. Our findings suggest an association between mitochondrial genetic burden and aSyn seeding. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
DOI
10.1002/mds.70553
PMID
42806694
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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