Disease-related patterns of in vivo pathology in Corticobasal syndrome

PURPOSE: To assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer’s disease. METHODS: We assessed tau aggregates with [(18)F]AV1451 PET, amyloid-β depositions with [(18)F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [(18)F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [(18)F]AV1451 binding. RESULTS: CBS patients showed increases in [(18)F]AV1451 SUVRs in parietal (P < 0.05) and frontal (P < 0.05) cortices in the affected hemisphere compared to healthy controls and in precentral (P = 0.008) and postcentral (P = 0.034) gyrus in the affected hemisphere compared to MCI patients. Our data were confirmed at the histopathological level in one CBS patient who underwent brain biopsy and showed sparse tau pathology in the parietal cortex co-localizing with increased [(18)F]AV1451 signal. Cortical and subcortical [(18)F]AV45 uptake was within normal levels in CBS patients. In parietal and frontal cortices of the most affected hemisphere we found also grey matter loss (P < 0.05), increased mean diffusivity (P < 0.05) and decreased fractional anisotropy (P < 0.05) in CBS patients compared to healthy controls and MCI patients. Grey matter loss and white matter changes in the precentral gyrus of CBS patients were associated with worse motor symptoms. CONCLUSIONS: Our findings demonstrate disease-related patterns of in vivo tau and microstructural pathology in the absence of amyloid-β, which distinguish CBS from non-affected individuals and MCI patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-018-4104-2) contains supplementary material, which is available to authorized users.