Presymptomatic Altered White Matter Diffusivity in Inherited Prion Disease

Harpreet Hyare¹, Enrico De Vita², Gerard R. Ridgway¹, Marie-Claire Porter¹, Peter Rudge¹, Tarek A. Yousry², Simon Mead¹, John Collinge³, John Thornton²

We present the application of voxel-based analysis of diffusion tensor imaging (DTI) and voxel-based morphometry in the largest cohort of presymptomatic mutation carriers of prion disease and symptomatic patients with a range of human prion diseases. We observed presymptomatic increased fractional anisotropy (FA) in functionally relevant white matter (WM) tracts whereas decreased FA was seen in symptomatic patients. Our findings could be due to propagation of the abnormal prion protein along white matter tracts before the other pathological hallmarks of prion disease that cause loss of WM integrity are evident.