Influence of the prion protein and the apolipoprotein E genotype on the Creutzfeldt-Jakob Disease phenotype

We investigated the risk associated with the codon 129 polymorphism in the prion protein gene (PRNP) and apolipoprotein E gene (APOE) isoforms for dev elopment of Creutzfeldt-Jakob disease (CJD) (n = 126) and the possible infl uences on the disease pathology and its most important clinical characteris tics. The PRNP M129V (PRNP129) polymorphism was determined using both DNA e xtracted from formalin fixed and paraffin embedded brain tissue (n = 59) an d leukocyte extracted DNA (n = 67). In the latter group also the PRNP open reading frame and the APOE genotype were analysed and compared to a neurolo gically unaffected, age and sex matched control group (n = 79). We found th at methionine homozygosity of the PRNP129 increases the risk for developing CJD. PRNP129 also influenced the prion accumulation patterns in brain. The APOE 4 allele was an independent risk factor for developing CJD. We furthe r observed a significant dose dependent APOE 4 effect on the number and typ e of amyloid-beta plaques in the brain of CJD patients. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.