Imaging Tau Pathology in Parkinsonisms
Centre for Addiction and Mental Health
As we enter the era of precision medicine, and in the absence of reliable disease-specific markers, it is necessary to identify probes helping discriminating tauopathies from synucleinopathies, particularly in the early course of the disease, as diseasemodifying therapies become available. Recently, a new generation of tau radioligand (i.e. [18F]MK-6240), not suffering from most of previous tracers’ limitations, has shown very encouraging results for tau aggregations associated with Alzheimer’s disease. To date, no studies have been reported with [18F]MK-6240 in non-AD tau pathology, in various forms of parkinsonism. The objective of this pilot project is to perform a set of PET-studies using this last generation of tau radiotracer, i.e. [18F]MK-6240, as in-vivo proxy of tau protein deposition in progressive supranuclear palsy (PSP), cortical-basal-degeneration (CBD) and possibly Parkinson’s disease dementia (PDD). This translational data set will offer a unique opportunity to identify robust biomarkers which may accurately characterize these devastating neurodegenerative diseases.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
If successful, this novel tracer may have very important implications at several levels. In fact, we could envisage the use of this new biomarker as:
i) an indicator of disease severity,
ii) a possible tool for early detection of disease progression,
iii) assessment instrument for interventional medicine for neuro-protection studies.
We anticipate that this new probe, i.e. [18F]MK-6240, may be able to quantify tau burden in PSP, CBD and PDD, and to identify vulnerable neuroanatomical networks in PSP, CBD, and PDD with increased tau uptake and potential relationship with clinical expression of motor and non-motor symptoms. We predict that tau deposition in PSP, CBD and PDD patients will differ anatomically and in the degree of cortical/subcortical pathology, possibly correlating with disease severity.