Study Rationale: Forms of alpha-synuclein, the protein that aggregates in Parkinson’s disease (PD), can be detected in cerebrospinal fluid (CSF) by seed amplification assays (SAA). These highly accurate tests can diagnose alpha-synuclein pathology, even at very early stages of disease. Alpha-synuclein also accumulates in the brains of people with Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB). This project will use SAA to study alpha-synuclein pathology in people with normal cognition, mild cognitive changes and DLB, to assess how alpha-synuclein aggregates affect cognition and other symptoms and how alpha-synuclein and AD pathology interact.
Hypothesis: We hypothesize that having both alpha-synuclein aggregation and AD pathology will lead to more noticeable effects on cognition, movement and behavior than will either pathology on its own.
Study Design: We will obtain alpha-synuclein SAA data from large groups of people followed by several different research centers, together with extensive data on the participants’ clinical symptoms and cognitive performance as measured annually. We also will obtain data from people who underwent CSF SAA testing during life and allowed their brains to be examined after death. We will analyze how common positive CSF SAA tests are among cognitively unimpaired people and people with mild cognitive impairment. We will explore how the combination of CSF SAA and AD pathology influence these changes.
Impact on Diagnosis/Treatment of Parkinson’s disease: CSF SAA testing allows diagnosis of people at risk for PD or DLB at very early stages, even before symptoms arise. This project will help to identify those who may be at highest risk. Early and accurate diagnosis can pave the way for studies of new preventatives or early treatments.
Next Steps for Development: If successful, the findings of this study can be used to improve the accuracy of diagnosis of PD and DLB and to provide a clearer understanding of who may progress and show cognitive changes.