Abstract

Parkinson's disease is a neurodegenerative disorder characterized by motoric dysfunction and a range of non-motoric disturbances. Neuropathologically, it features prominent neuronal loss in specific areas of the brain as well as characteristic alpha-synuclein protein inclusions called Lewy bodies. In recent years, smaller types of alpha-synuclein aggregates not organized into Lewy bodies have been hypothesized to be highly involved in disease pathogenesis, though few studies have shown these aggregates in tissue samples, mainly due to technical limitations.

In this PhD project, carried out at Aarhus University, we developed a novel alpha-synuclein proximity ligation assay to detect such small aggregates in cell models and post-mortem human tissue sections. We compared the results from our new assay with traditional immunohistochemistry to detect Lewy bodies and show that our assay detects more pathology at much earlier timepoints in disease. We also demonstrate that a genetic variant of Parkinson's disease without Lewy bodies - a curiosity currently left unexplained - does contain the smaller types of aggregates, pointing to a common disease mechanism. Lastly, we investigated the temporal development of phosphorylation at serine-129 of alpha-synuclein, a common disease marker, and examined the potential of its inhibition as a treatment target.

The defence is public and takes place on 16/5 at 13.00 in AIAS auditorium, Aarhus University, Høegh-Guldbergs Gade 6B, 8000 Aarhus C. The title of the project is "Investigating markers of inclusion and non-inclusion α-synuclein aggregate pathology in Parkinson’s disease and related disorders".

For more information, please contact PhD student Nanna Møller Jensen, email: nanna.mj@biomed.au.dk, Phone +45 6022 6553.