Phenotypic characteristics of familial Creutzfeldt‐Jakob disease assoicated with the codon 178AsnPRNP mutation

Abstract

A group of 43 patietns from seven families affected by Creutzfeldt‐Jakob disease (CJD) with the codon 178^Asn mutation of the PRNP amyloid precursor gene is compared to a group of 211 patients with the sporadic form of the disease. As a group, the patients with codon 178^Asn mutation had an earlier age at onset of illness (almost always presenting as an insidious loss of memory), a longer duration of illness, and an absence of periodic electroencephalographic activity. Transmission of disease to primates was accomplished using brain tissue homogenates from 6 of 10 patients, resulting in significantly shorter incubation periods than those due to sporadic CJD inocula. These findings are interpreted and discussed in terms of possible differences in the temporospatial evolution of damage to the brain, and of accelerated induction of polymerized amyloid protein by its mutationally altered template precursor.