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BackgroundProgressive supranuclear palsy (PSP) is a common cause of atypical parkinsonism.ObjectiveTo study the genetic and clinico-pathological profile of various PSP phenotypes using patient data from the PROSPECT-UK study.MethodsClinical data from PSP patients in the PROSPECT-UK study was analysed to assess the rates of various PSP phenotypes, as defined by the 2017 Movement Disorder Society diagnostic criteria. A subset of patients are currently undergoing 5 year longitudinal follow-up, including genetics, video clinical assessments and post-mortem confirmation of diagnosis.ResultsWe have established a cohort of 345 patients with PSP. The longitudinal sub-cohort consists of 100 PSP patients: 58 patients with classical Richardson’s syndrome (RS) and 42 patients with a variety of non-RS presentations including PSP-Parkinsonism and Pure Akinesia with Gait Freezing. We found significant differences in the mean disease duration of deceased RS and non-RS cases (5.6 vs 9.2 years) but similar rates of PSP pathology in cases (n=28) with post-mortem confirmation (94% and 100%). Our PROSPECT-UK data has contributed to a GWAS which identified that common variation at the TRIM11 locus determined PSP phenotype (Jabbari et al 2018). In addition, we have identified 1 case with a MAPT L284R mutation and 1 case with genetic and biochemically confirmed Niemann-Pick type C disease.ConclusionsThe PROSPECT-UK study has furthered our knowledge on the clinical profile of PSP and the biological determinants which drive phenotypic variation.

BackgroundThere are a number of different causes of corticobasal syndrome (CBS) and we are recruiting CBS patients across the UK to the PROSPECT-UK study.ObjectiveTo define patients with CBS and to define features that are helpful in determining the underlying pathological diagnosis.MethodsThe RaDAR platform enables the recruitment of patients with CBS. Eligible patients are anonymously invited to contact the study team. Following informed consent, patients can participate remotely or be seen at their local study site. A subset of these patients undergo deep phenotyping, including CSF analysis for total Tau and Abeta.ResultsWe have established a cohort of 179 patients with CBS for future therapeutic, biomarkers and clinical studies. Mean recruitment is 5/month. The ABN RaDAR scheme has identified 58 CBS patients across the UK through 2018 so far, and we are liaising with consultants to recruit these patients. Deep phenotyping is underway – in patients with CSF analysis, 47% have an Alzheimer disease–like CSF profile highlighting the phenotypic diversity in this group. We are continuing to analyse other features of CBS.ConclusionsWe are continuing to define the diverse pathological causes of CBS with a view to developing future disease modifying treatment trials.