Familial Creutzfeldt-Jakob disease in a patient carrying both a presenilin1 missense substitution and a prion protein gene insertion

We describe a patient who was clinically diagnosed with familial early-onse t Alzheimer disease (AD) carrying both the E318G substitution in presenilin 1 (PSEN1) and an insertion of 7 octapeptide coding repeats in the prion pr otein gene (PRNP). Neuropathological examination revealed elongated cerebel lar prion protein deposits in the absence of AD pathology. Further analysis of other family members showed that the Creutzfeldt-Jakob disease phenotyp e in this family was caused solely by the PRNP insertion. This observation is consistent with our previous finding that PSEN1 E318G is not causally re lated to AD.