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Acta Neuropathologica

, Volume 135, Issue 2, pp 201–212 | Cite as

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

  • Charles DuyckaertsEmail author
  • Véronique Sazdovitch
  • Kunie Ando
  • Danielle Seilhean
  • Nicolas Privat
  • Zehra Yilmaz
  • Laurène Peckeu
  • Elodie Amar
  • Emmanuel Comoy
  • Aleksandra Maceski
  • Sylvain Lehmann
  • Jean-Pierre Brion
  • Jean-Philippe Brandel
  • Stéphane HaïkEmail author
Original Paper

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

Creutzfeldt–Jakob disease Abeta pathology Tau pathology Alzheimer’s disease Transmission Prions Growth hormone 

Notes

Acknowledgements

This work was supported by Santé Publique France (CNR-ATNC) and by the program “Investissements d’avenir” (ANR-10-IAIHU-06).

Author contribution

C.D., V.S., D.S., and S.H. performed neuropathological and biochemical diagnoses and analyzed the data. L.P., J.P. Bra., and S.H. diagnosed and recruited the patients and contributed to the clinical analyses. K.A., Z.Y., and J.P. Bri. performed Gallyas staining, double staining with Gallyas and tau and Western blot analyses of tau. N.P., V.S., C.D., and S.H. performed tau, PrP and Abeta immunohistochemistry and analyzed results. E.A. performed PRNP and ApoE genotyping. E.C., A.M., and S.L. performed the hormone batch study. C.D. and S.H. oversaw the study, analyzed data, and drafted the manuscript with contributions from all authors.

Supplementary material

401_2017_1791_MOESM1_ESM.pdf (143 kb)
Supplementary material 1 (PDF 142 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Charles Duyckaerts
    • 1
    • 2
    Email author
  • Véronique Sazdovitch
    • 1
    • 2
  • Kunie Ando
    • 3
  • Danielle Seilhean
    • 1
    • 2
  • Nicolas Privat
    • 1
  • Zehra Yilmaz
    • 3
  • Laurène Peckeu
    • 1
  • Elodie Amar
    • 4
  • Emmanuel Comoy
    • 5
  • Aleksandra Maceski
    • 6
  • Sylvain Lehmann
    • 6
  • Jean-Pierre Brion
    • 3
  • Jean-Philippe Brandel
    • 1
    • 7
  • Stéphane Haïk
    • 1
    • 2
    • 7
    Email author
  1. 1.Inserm U1127, CNRS UMR 7225, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinièreSorbonne UniversitésParisFrance
  2. 2.Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Pitié-SalpêtrièreAP-HPParisFrance
  3. 3.Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, ULB Neuroscience InstituteUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Service de Biochimie et Biologie Moléculaire, Hôpital LariboisièreAP-HPParisFrance
  5. 5.Commissariat à l’Energie Atomique, DRF/iMETI/SEPIAFontenay-aux-RosesFrance
  6. 6.Laboratoire de Biochimie Protéomique Clinique, CHU de Montpellier, CRB, INSERM U1183Université de MontpellierMontpellierFrance
  7. 7.Hôpital de la Pitié-Salpêtrière, Cellule nationale de référence des MCJAP-HPParisFrance

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