Iatrogenic Creutzfeldt-Jakob disease with Amyloid-β pathology: an international study

Acta Neuropathologica Communications

Steven J. Collins¹  Catriona A. McLean²  Piero Parchi³  Tetsuyuki Kitamoto⁴  Han Wang⁵  Maurizio Pocchiari⁶  Brian S. Appleby⁷  Diane Kofskey⁸  Jiri G. Safar⁸  Ignazio Cali⁸  Pierluigi Gambetti⁸  Mark L. Cohen⁸  Ryan A. Maddox⁹  Ermias D. Belay⁹  Lawrence B. Schonberger⁹  Giorgio Giaccone^1,10  Fabrizio Tagliavini^1,10  Jean-Philippe Brandel^1,11  Nicolas Privat^1,11  Charles Duyckaerts^1,11  Stéphane Haїk^1,11  Véronique Sazdovitch^1,11  Ellen Leschek^1,12 

[1] Australian National Creutzfeldt-Jakob Disease Registry, Department of Medicine, and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne;Department of Anatomical Pathology, Alfred Health;Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna;Department of Neurological Science, Tohoku University Graduate School of Medicine;Department of Neurology, University Hospitals Cleveland Medical Center;Department of Neurosciences, Istituto Superiore di Sanità;Departments of Neurology, Case Western Reserve University, School of Medicine;Departments of Pathology, Case Western Reserve University, School of Medicine;Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention;Fondazione IRCCS, Istituto Neurologico Carlo Besta;Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière;National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services;

关键词: Amyloid-β;    Pathology;    iCJD;    Cerebral amyloid angiopathy;    Thioflavin S;   

DOI  :  10.1186/s40478-017-0503-z

来源: DOAJ

【 摘 要 】

Abstract The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts. To investigate this phenomenon further, a cohort of 27 iCJD cases – 21 with adequate number of histopathological sections – originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrPSc), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND). Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrPSc with the exception of iCJD harboring the “MMi” phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Aβ pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients’ younger age CAA was more severe in iCJD than sCJD, while Aβ diffuse plaques, in absence of Aβ CP, populated one third of sCJD. Aβ pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD. In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Aβ phenotypes indicating that the occurrence of Aβ pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Aβ phenotype in iCJD since it is observed in nearly 90% of all iCJD with Aβ pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Aβ pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.

【 授权许可】

Unknown