IDENTIFICATION OF THE PRION PROTEIN ALLOTYPES WHICH ACCUMULATE IN THEBRAIN OF SPORADIC AND FAMILIAL CREUTZFELDT-JAKOB-DISEASE PATIENTS

A characteristic feature of Creutzfeldt-jakob disease (CJD) is the acc umulation in the brain of the amyloid protease-resistant protein PrPre s. PrPres derives from a host-encoded, protease-sensitive isoform, PrP sen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methionine or valine residue at the pol ymorphic position 129 may be critical in sporadic CJD cases. We found that in the brain of patients heterozygous for the mutation in which i soleucine is substituted for valine at codon 210 (Val210Ile), the PrPr es is formed by both the wild-type and mutant PrPsen. We also found th at in a sporadic CJD patient, who was heterozygous (Met/Val) at positi on 129, PrPres is also formed by both allotypes. These data associate transmissible spongiform encephalopathies with other amyloidosis, alth ough the nature of the transmissible agent remains unsettled.