Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology

Acta Neuropathol. 2018 Feb;135(2):201-212. doi: 10.1007/s00401-017-1791-x. Epub 2017 Nov 22.

Abstract

Abeta deposits and tau pathology were investigated in 24 French patients that died from iatrogenic Creutzfeldt-Jakob disease after exposure to cadaver-derived human growth hormone (c-hGH) in the 1980s. Abeta deposits were found only in one case that had experienced one of the longest incubation periods. Three cases had also intracellular tau accumulation. The analysis of 24 batches of c-hGH, produced between 1974 and 1988, demonstrated for the first time the presence of Abeta and tau contaminants in c-hGH (in 17 and 6 batches, respectively). The incubation of prion disease was shorter in the French patients than the incubation times reported in two previously published British series. We interpreted the low incidence of Abeta in this French series as a consequence of the shorter incubation period observed in France, as compared to that observed in the United Kingdom. This concept suggested that a mean incubation period for the development of detectable Abeta deposits would be longer than 18 years after the first exposure. Moreover, we hypothesized that tau pathology might also be transmissible in humans.

Keywords: Abeta pathology; Alzheimer’s disease; Creutzfeldt–Jakob disease; Growth hormone; Prions; Tau pathology; Transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Brain / pathology*
  • Cadaver
  • Cohort Studies
  • Creutzfeldt-Jakob Syndrome / metabolism
  • Creutzfeldt-Jakob Syndrome / pathology*
  • Creutzfeldt-Jakob Syndrome / transmission*
  • Drug Contamination*
  • France
  • Human Growth Hormone* / administration & dosage
  • Humans
  • Iatrogenic Disease
  • Immunoassay
  • Infectious Disease Incubation Period
  • Prion Proteins / genetics
  • Prion Proteins / metabolism
  • Young Adult
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • MAPT protein, human
  • PRNP protein, human
  • Prion Proteins
  • tau Proteins
  • Human Growth Hormone