Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 146 No. 0304 (2016)

Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

  • Karl Frontzek
  • Mirjam I. Lutz
  • Adriano Aguzzi
  • Gabor G. Kovacs
  • Herbert Budka
DOI
https://doi.org/10.4414/smw.2016.14287
Cite this as:
Swiss Med Wkly. 2016;146:w14287
Published
17.01.2016

Summary

QUESTIONS UNDER STUDY: Alzheimer-type amyloid-β (Aβ) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Aβ by the treatment. Here we investigated the prevalence of Aβ pathology in other instances of iCJD related to dura mater grafts.

METHODS: By use of immunohistochemistry for Aβ, we investigated seven brains of patients (age range 28–63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40–63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55–85 years) with the same methods.

RESULTS: In five of seven iCJD brains, Aβ was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0.001) more frequent than in the age-matched sCJD controls and in the usual sCJD series.

CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting. The presence of Aβ pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Aβ aggregates from the grafts to host tissues.

References

  1. Ashe KH, Aguzzi A. Prions, prionoids and pathogenic proteins in Alzheimer disease. Prion. 2013;7(1):55–9.
  2. Knowles TPJ, Waudby CA, Devlin GL, Cohen SIA, Aguzzi A, Vendruscolo M, et al. An analytical Solution to the kinetics of breakable filament assembly. Science. 2009;326(5959):1533–7.
  3. Budka H, Will RG. The end of the BSE saga: do we still need surveillance for human prion diseases? Swiss Med Wkly. 2015;145:w14212.
  4. Büeler H, Aguzzi A, Sailer A, Greiner R-A, Autenried P, Aguet M, et al. Mice devoid of PrP are resistant to scrapie. Cell. 1993;73:1–20.
  5. Eisele YS, Obermüller U, Heilbronner Gt, Baumann F, Kaeser SA, Wolburg H, et al. Peripherally applied Aβ-containing inoculates induce cerebral β-amyloidosis. Science. 2010;330(6006):980–2.
  6. Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 2013;501(7465):45–51.
  7. Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet. 2013;47:601–23.
  8. Jucker M, Walker LC. Neurodegeneration: Amyloid-β pathology induced in humans. Nature. 2015;525(7568):193–4.
  9. Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S, Hench Jr, et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci U S A. 2013;110(23):9535–40.
  10. Lewis J, Dickson DW. Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. Acta Neuropathol. 2016;131(1):27–48.
  11. Lee S-J, Masliah E. Neurodegeneration: Aggregates feel the strain. Nature. 2015;522(7556):296–7.
  12. Bae E-J, Yang N-Y, Song M, Lee CS, Lee JS, Jung BC, et al. Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein. Nat Commun. 2014;5.
  13. Amschl D, Neddens J, Havas D, Flunkert S, Rabl R, Römer H, et al. Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model. BMC Neurosci. 2013;14(1):1–14.
  14. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, et al. Pathological α-synuclein transmission initiates parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949–53.
  15. Jaunmuktane Z, Mead S, Ellis M, Wadsworth JDF, Nicoll AJ, Kenny J, et al. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature. 2015;525(7568):247–50.
  16. Preusser M, Ströbel T, Gelpi E, Eiler M, Broessner G, Schmutzhard E, et al. Alzheimer-type neuropathology in a 28 year old patient with iatrogenic Creutzfeldt-Jakob disease after dural grafting. J Neurol Neurosurg Psychiatry. 2006;77(3):413–6.
  17. Frontzek K, Moos R, Schaeper E, Jann L, Herfs G, et al. Iatrogenic and sporadic Creutzfeldt-Jakob disease in two sisters without mutation in the prion protein gene. Prion. 2015;9(6):444–8.
  18. Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005;64(9):1586–91.
  19. Schellenberg GD, Montine TJ. The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathol. 2012;124(3):305–23.
  20. Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, et al. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol. 2013;70(4):462–8.

Most read articles by the same author(s)