An update of the epidemiology of sporadic Creutzfeldt-Jakob disease in Italy based on neuropathologic and molecular typing of a large cohort of patients

Despite its proven heterogeneity, sporadic CJD (sCJD) to date has been only analyzed epidemiologically as a single entity. Taking advantage of the current high autopsy rate for clinically suspected CJD cases, we evaluated the frequency of sCJD subtypes in Italy in a large cohort of consecutive cases. Inclusion criteria were onset of symptoms within the period 2000 \u2013 2005 and neuropathologic disease confirmation. Patients carrying pathogenic mutations in the coding region of PRNP and/or having a positive family history were excluded. PRNP genotyping was performed in 402 (87.9%) cases and showed 283 (70.4%) MM, 62 (15.4%) MVand 57 (14.2%) VV subjects. Most cases belonged to MM/MV1 (51%), mixed MM/MV1+2C (22%), VV2 (15%) and MV2 (8%) subtypes, while the remaining 4% comprised rare variants or atypical cases. Our study provides the first estimate of the incidence of the sCJD variants in a large cohort of consecutive patients and the basis for the study of spatial and temporal sCJD clustering in Italy