Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease

N Engl J Med. 2003 Nov 6;349(19):1812-20. doi: 10.1056/NEJMoa030351.

Abstract

Background: In patients with sporadic Creutzfeldt-Jakob disease, pathologic disease-associated prion protein (PrPSc) has been identified only in the central nervous system and olfactory-nerve tissue. Understanding the distribution of PrPSc 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 PrPSc 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 PrPSc in extraneural organs of 36 patients with sporadic Creutzfeldt-Jakob disease who died between 1996 and 2002.

Results: PrPSc was present in the brain tissue of all patients. In addition, we found PrPSc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrPSc in both spleen and muscle specimens. Patients with extraneural PrPSc 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 PrPSc.

Conclusions: Using sensitive techniques, we identified extraneural deposition of PrPSc in spleen and muscle samples from approximately one third of patients who died with sporadic Creutzfeldt-Jakob disease. Extraneural PrPSc appears to correlate with a long duration of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Brain / metabolism
  • Brain / pathology
  • Creutzfeldt-Jakob Syndrome / metabolism*
  • Creutzfeldt-Jakob Syndrome / pathology
  • Humans
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • PrPSc Proteins / metabolism*
  • Prions / genetics
  • Spleen / metabolism*
  • Spleen / pathology

Substances

  • PrPSc Proteins
  • Prions