Tau imaging in parkinsonian disorders
University of British Columbia
We plan to use positron emission tomography (PET) to differentiate between Parkinson’s disease (PD) and other conditions that cause features of parkinsonism but which have different pathology, are less responsive to medication and are associated with a more aggressive course. Differentiating these disease from PD can be extremely challenging, yet the implications may be significant. We will use newly developed tools to image abnormal deposition of tau protein in the brains of people with these disorders. We will also use these tools to see if there are differences in tau deposition between PD patients with intact cognition and those with cognitive problems. Finally, because tau may interact with other proteins that are abnormally deposited in PD, we will study tau deposition in people who have a genetic mutation that places them at high risk of going on to develop PD in the future. We will use PET to determine whether tau deposition is associated with abnormal inflammation in the brain and whether the two processes progress in tandem. This work will have an impact on the development of better diagnostic tools and also on understanding the mechanisms contributing to Parkinsonian disorders and their complications.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
This work may help develop better diagnostic tools. The ability to differentiate between the conditions studied here is important for prognosis and for selection of participants in clinical trials. Assessment of tau in cognitive problems associated with Parkinson’s disease (PD) will improve our understanding of this common complication and help guide therapies. Knowledge of how tau deposition evolves in PD will shed insight on disease mechanisms, help predict future complications and ultimately suggest better approaches to slow disease progression. While the focus of the proposal is on PD and related conditions, the findings will be relevant to other tau disorders.
We anticipate that tau imaging (i) will differentiate between PD and atypical PD-like disorders such as progressive supranuclear palsy and multiple system atrophy; (ii) will show differences between PD patients with and without cognitive impairment; (iii) that tau deposition will be associated with abnormal brain inflammation and (iv) that abnormal tau deposition will progress in an orderly manner as disease progresses from its earliest to more advanced stages.