α-Synuclein pathology beyond Lewy-related pathology: α-synuclein oligomers and seeding activity in LRRK2-related Parkinson’s disease

Project title: α-Synuclein pathology beyond Lewy-related pathology: α-synuclein oligomers and seeding activity in LRRK2-related Parkinson’s disease 

Principal Investigator:  

Hiroaki Sekiya M.D., Ph.D. 

Co-Principal Investigators& Institutions: Dennis Dickson (Mayo Clinic Jacksonville), Luis Concha (Amprion,  Yuhong Fu and Glenda Halliday (University of Sydney), Poul Jensen and Nanna Moller Jensen (Arhaus University)

Principal Investigator institution: Mayo Clinic Rochester

Summary of the project:  

LRRK2-related Parkinson’s disease (LRRK2-PD) shows clinical similarities to sporadic PD but often lacks Lewy-related pathology (LRP) and can test negative in seed amplification assays (SAA).  

Recent evidence suggests that α-synuclein (αSYN) oligomers are present in all LRRK2-PD cases, even those without LRP, indicating a potential common pathological feature. This project will investigate the link between αSYN oligomers and their seeding activity by analysing postmortem brain tissue using proximity ligation assay (PLA) and SAA across multiple labs.  

It aims to assess detection consistency, antibody specificity, and the relationship between oligomers and seeding capacity. The results could standardize SAA methods, improve biomarker development, and enable better patient stratification for precision therapies in Parkinson’s disease. 

Project duration: 12 months