To date, mutations at 34 different sites in the human prion protein gene are associated with development of genetic prion diseases in an autosomal dominant pattern with heterogeneous phenotypes . However, genetic prion diseases do not always fit precisely within the classical definition of prion disease, i.e. rapid clinical decline, spongiform degeneration, gliosis and presence of partially protease-resistant PrP. In contrast, genetic prion diseases usually display prolonged clinical course, variable spongiform degeneration, variation in the molecular size of PrP detected in disease-associated deposits, and presence of abnormal PrP in an amyloid form. Genetic prion diseases can be subdivided into different groups based on clinical/pathological characteristics. These include genetic/familial CJD, Gerstmann-Sträussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). GSS disease is unusual in that PrPSc is mostly in the amyloid form which is deposited either as multifocal amyloid plaques in the neuropil or as perivascular plaques consistent with cerebral amyloid angiopathy (CAA) . In GSS and PrP-CAA, immunoblotting reveals proteinase K (PK)-resistant PrP bands approximately 7–8 kD in size which correlate with the presence of amyloid PrPSc and are distinct from the larger bands usually seen in genetic CJD or FFI [31, 33, 42].