The apolipoprotein E alleles as major susceptibility factors for Creutzfeldt-Jakob disease

Abstract

SummaryCreutzfeldt-Jakob disease (CJD) is a rapid progressive mental and neurological disorder characterised by dementia and is both infectious and genetic. Pathogenic mutations and a predisposing polymorphism have been described in the prion protein gene and an abnormal prion product accumulates in the brain of affected patients. Apolipoprotein E (APOE), a protein of lipid metabolism, has been detected in some prion protein deposits. This ApoE exists as three common isoforms, coded by specific allele (∈2, ∈3, ∈4). The presence of at least one ∈4 allele was described as a major risk factor for Alzheimer's disease, another neurodegenerative disorder. From a series of 61 patients with CJD we found that ∈4 allele of the APOE gene was a risk factor for the disease (p < 0·01). This association was observed in both definite and probable cases, and for patients with and without prion protein gene mutations. Moreover, in affected subjects, ∈2 allele of the APOE gene delayed occurrence of death (p<0·01) independently of other known mutations influencing the phenotype of the disease.These effects on neurodegenerative disease associated with APOE alleles suggest a strong involvement of the APOE locus in brain metabolism.