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Acta Neuropathologica
Published in: Acta Neuropathologica 2/2017

Open Access 01-08-2017 | Original Paper

Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK

Authors: Diane L. Ritchie, Peter Adlard, Alexander H. Peden, Suzanne Lowrie, Margaret Le Grice, Kimberley Burns, Rosemary J. Jackson, Helen Yull, Michael J. Keogh, Wei Wei, Patrick F. Chinnery, Mark W. Head, James W. Ironside

Published in: Acta Neuropathologica | Issue 2/2017

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Abstract

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.
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Metadata
Title
Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK
Authors
Diane L. Ritchie
Peter Adlard
Alexander H. Peden
Suzanne Lowrie
Margaret Le Grice
Kimberley Burns
Rosemary J. Jackson
Helen Yull
Michael J. Keogh
Wei Wei
Patrick F. Chinnery
Mark W. Head
James W. Ironside
Publication date
01-08-2017
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 2/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-017-1703-0

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