Study Rationale:
The precise mechanisms of cellular damage in Parkinson's disease remain unclear. Research has shown that abnormal forms of the protein alpha-synuclein accumulates in brain cells in most people with Parkinson's. In many other neurodegenerative diseases, the protein tau accumulates in brain cells, causing damage. Some evidence suggests that tau may also accumulate in brain cells in at least in some people with Parkinson's, particularly those with a mutation in the gene LRRK2. The team will use recent advances in imaging brain tau to investigate tau deposition in Parkinson's patients with and without LRRK2 mutations.
Hypothesis:
The team will use MK-6240 PET imaging to investigate whether tau can be measured in the brains of people with Parkinson's and a LRRK2 mutation and compared to people with Parkinson's without a LRRK2 mutation and control volunteers.
Study Design:
The team expects to enroll approximately 30 subjects in this study, including up to 10 each of (1) participants with Parkinson's and LRRK2 mutations, (2) participants with Parkinson's without a LRRK2 mutation, and (3) age-matched control participants. All subjects will be screened for eligibility, including standardized Parkinson's rating scales, DaTscan SPECT, and MRI (recent prior studies may be used). Eligible subjects will undergo PET imaging with the tau tracer [18F]MK-6240. Participates with PD without a LRRK2 mutation could be early or later in their disease. If the initial subjects with a LRRK2 mutation demonstrate sufficient tau signal, then subjects with a LRRK2 mutation but without motor symptoms will also undergo imaging as part of that group.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
If tau can be seen and measured in the brain in at least a subset of individuals with Parkinson's, then tau could be a target for scientific and potential therapeutic investigations. People with Parkinson's and a LRRK2 mutation appear to be particularly at risk to accumulate pathological tau deposits. This is a preliminary study to determine if this tracer, [18F]MK-6240, can be used to visualize these tau deposits.
Next Steps for Development:
If [18F]MK-6240 PET imaging does reveal tau deposits in some people with Parkinson's, then this imaging tool could be used to identify them and follow their disease progression. This could also help identify people appropriate for participation in tau therapeutic trials, similar to those underway for Alzheimer's disease. This would also help to dissect the molecular processes that underlie Parkinson's disease. This is particularly relevant to those with LRRK2 mutations.