The present study reports the results of a comprehensive analysis of all major available CSF biomarkers for the differential diagnosis of CJD in a large unselected clinical population reflecting clinical practice, taking also into account the effect of the disease subtype on diagnostic accuracy and the influence of tau and Aβ brain pathology on p-tau and Aβ42 CSF levels. This evidence concerns the gene MAPT and Creutzfeldt Jacob disease.