Extraneural Pathologic Prion Protein in Sporadic Creutzfeldt–Jakob Disease

Abstract

BACKGROUND: In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrP Sc ) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrP Sc in Creutzfeldt-Jakob disease is important for classification and diagnosis and perhaps even for prevention. METHODS: We used a highly sensitive method of detection - involving the concentration of PrP Sc by differential precipitation with sodium phosphotungstic acid, which increased the sensitivity of Western blot analysis by up to three orders of magnitude - to search for PrP Sc in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002. RESULTS: PrP Sc was present in the brain tissue of all patients. In addition, we found PrP Sc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrP Sc in both spleen and muscle specimens. Patients with extraneural PrP Sc had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic Creutzfeldt-Jakob disease than were patients without extraneural PrP Sc . CONCLUSIONS: Using sensitive techniques, we identified extraneural deposition of PrP Sc in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrP Sc appears to correlate with a long duration of disease.