Grant: Master's Award: Canada Graduate Scholarships

One of the defining characteristics of Parkinson's disease (PD) is the aggregation of a protein found in the brain called alpha-synuclein (AS). In 2000, we discovered that an antibody (CS1-4)created to react with LMP1 - a protein from Epstein-Barr Virus (EBV) which naturally infects over 90% of humans - also interacts with alpha-synuclein. We proposed the possibility that antibodies produced after EBV infection could cross-react with AS and cause its aggregation, perhaps even precipitating PD. In follow-up experiments, there was no difference found in the levels of natural AS or LMP1 antibodies between PD patients and unaffected control patients. However, recent PD research has proven sustained high levels of antibodies unnecessary for the development of PD. It has been proposed that a "single hit" of AS aggregation in the nose or the gut can propagate neuron to neuron, spreading to the central nervous system and eventually the whole brain. We now propose that this initial aggregation may be caused by a natural LMP1 antibody. Since EBV infection generally happens at a young age and PD is a disease of the older adult, it is plausible that the antibody response fades over time and can no longer be detected once the clinical signs of PD are evident. We have found a region of similarity in the protein sequence of LMP1 and AS. We believe this is where any cross-reaction would occur. Since the sequence of AS in mice and humans diverges in this region, we can study the point by using wild-type (regular) mice and mice which have had their AS replaced with the human gene. First, we will take neurons from these mice and - in vitro - add CS1-4 LMP1 antibodies and use fluorescence microscopy to search for initial signs of AS aggregation. If these experiments succeed, we will proceed to administering CS1-4 to live mice with human or mouse AS to examine AS aggregation in vivo. These experiments provide valuable insight into a possible viral cause of PD.