Infections and the Risk of Parkinson's Disease - PROJECT SUMMARY Parkinson’s disease (PD) is an incapacitating neurological disorder for which there is no effective treatment that can halt or reverse the progression. The lack of effective treatments is due in part to the poor understanding of the causes of this condition. Interestingly, it has been proposed that infections may play a role in causing PD. This hypothesis is supported by the fact that infections can cause other neurological diseases, such as multiple sclerosis, and by evidence from some scientific studies suggesting a potential link between specific microbes, such as Influenza viruses, and PD. Although some of the evidence is tantalizing, scientific studies have not generated consistent results, and had important limitations in their design (e.g., lack of information on factors that may alternatively explain a link between infections and PD). We propose to address these limitations by conducting a comprehensive investigation into the role of infections in the development of PD and non-motor PD signs and symptoms (e.g., constipation, smell loss) that often appear before the disease is clinically diagnosed. The study will take advantage of data and blood samples that have been prospectively collected from thousands of individuals who participate in two large studies: the Nurses’ Health Study, and the Health Professionals Follow- up Study. These individuals have been followed for several decades, and we have identified those who developed PD during this time. Our study population will comprise a subset of 120 individuals who developed PD and whose blood sample was taken before PD diagnosis and a similar group of 120 individuals who did not develop PD during follow-up. We will use a state-of-the-art laboratory method to measure the immune response to over 1800 proteins mapping to 160 virus and bacteria. The proposed project stands to produce groundbreaking results on the potential role of viral and bacterial infections in PD etiology, setting the stage for larger and more comprehensive epidemiological investigations. Most importantly, the information generated by the proposed project could lead to the development of novel treatments for PD.