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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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Inserm U1127, CNRS UMR 7225, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Sorbonne Universités, 47 boulevard de l’Hôpital, 75013, Paris, France

    Charles Duyckaerts, Véronique Sazdovitch, Danielle Seilhean, Nicolas Privat, Laurène Peckeu, Jean-Philippe Brandel & Stéphane Haïk

  2. Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France

    Charles Duyckaerts, Véronique Sazdovitch, Danielle Seilhean & Stéphane Haïk

  3. Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, ULB Neuroscience Institute, Université Libre de Bruxelles, Brussels, Belgium

    Kunie Ando, Zehra Yilmaz & Jean-Pierre Brion

  4. Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, AP-HP, Paris, France

    Elodie Amar

  5. Commissariat à l’Energie Atomique, DRF/iMETI/SEPIA, Fontenay-aux-Roses, France

    Emmanuel Comoy

  6. Laboratoire de Biochimie Protéomique Clinique, CHU de Montpellier, CRB, INSERM U1183, Université de Montpellier, Montpellier, France

    Aleksandra Maceski & Sylvain Lehmann

  7. Hôpital de la Pitié-Salpêtrière, Cellule nationale de référence des MCJ, AP-HP, Paris, France

    Jean-Philippe Brandel & Stéphane Haïk

Authors
  1. Charles Duyckaerts
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  2. Véronique Sazdovitch
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  3. Kunie Ando
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  6. Zehra Yilmaz
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  10. Aleksandra Maceski
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  11. Sylvain Lehmann
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  13. Jean-Philippe Brandel
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  14. Stéphane Haïk
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Contributions

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.

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Correspondence to Charles Duyckaerts or Stéphane Haïk.

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Duyckaerts, C., Sazdovitch, V., Ando, K. et al. 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 135, 201–212 (2018). https://doi.org/10.1007/s00401-017-1791-x

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  • DOI: https://doi.org/10.1007/s00401-017-1791-x

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