Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease

BACKGROUND: In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrP(sup Sc)) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrP(sup 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(sup 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(sup Sc) in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002. RESULTS: PrP(sup Sc) was present in the brain tissue of all patients. In addition, we found PrP(sup Sc) in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrP(sup Sc) in both spleen and muscle specimens. Patients with extraneural PrP(sup 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(sup Sc). CONCLUSIONS: Using sensitive techniques, we identified extraneural deposition of PrP(sup Sc) in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrP(sup Sc) appears to correlate with a long duration of disease.