Study Rationale: Disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) share many similarities in their pathology. In particular, both involve accumulation of amyloid-β and alpha-synuclein proteins. Our recent studies using cells and preclinical models suggest that these proteins interact in a way that contributes to nerve cell damage, brain degeneration and worsening of disease. Understanding this interaction could help identify new ways to diagnose and treat these diseases, but we must first determine whether the proteins behave in a similar way in humans.
Hypothesis: We hypothesize that amyloid-β and alpha-synuclein interact in the brains of people with PD and AD, and that this interaction influences disease progression in terms of the clinical symptoms as well as on brain structure and function.
Study Design: We will analyze samples of cerebrospinal fluid from people with PD, dementia with Lewy bodies, AD, and healthy volunteers. Using these samples, we will measure specific proteins involved in the amyloid-β and alpha-synuclein pathway that we have uncovered to identify ‘molecular subtypes’ of disease. This analysis will help us understand how these proteins relate to disease symptoms and progression, particularly to rates of cognitive decline.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our project aims to uncover new biomarkers that can improve the diagnosis and monitoring of PD and related disorders, as well as AD. Understanding this molecular pathology could lead to the development of highly targeted treatments for this group of interconnected diseases.
Next Steps for Development: If successful, the next steps will include clinical trials to test new treatments targeting the amyloid-β and alpha-synuclein pathway. Additionally, further research will focus on refining the novel biomarkers we identify here for better diagnosis and tracking of disease progression.