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Acta Neuropathologica

, Volume 134, Issue 2, pp 221–240

First Online: 27 March 2017Received: 15 February 2017Revised: 15 March 2017Accepted: 18 March 2017


Human-to-human transmission of Creutzfeldt–Jakob disease CJD has occurred through medical procedures resulting in iatrogenic CJD iCJD. One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone hGH to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected 35 cases of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33-35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta Aβ protein associated with Alzheimer’s disease AD in the brains and cerebral blood vessels in 18-33 hGH-iCJD patients and for the first time in 5-12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy CAA, regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA.

KeywordsAmyloid β Iatrogenic Creutzfeldt–Jakob disease Human growth hormone Prion protein Cerebral amyloid angiopathy Neuropathology Electronic supplementary materialThe online version of this article doi:10.1007-s00401-017-1703-0 contains supplementary material, which is available to authorized users.

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Autor: Diane L. Ritchie - Peter Adlard - Alexander H. Peden - Suzanne Lowrie - Margaret Le Grice - Kimberley Burns - Rosemary J


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