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Acta Neuropathol. 2017 Aug;134(2):221-240. doi: 10.1007/s00401-017-1703-0. Epub 2017 Mar 27.

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

Author information

1
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, Deanery of Clinical Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. diane.ritchie@ed.ac.uk.
2
UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
3
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, Deanery of Clinical Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
4
Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.
5
Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
6
MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.

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.

KEYWORDS:

Amyloid β; Cerebral amyloid angiopathy; Human growth hormone; Iatrogenic Creutzfeldt–Jakob disease; Neuropathology; Prion protein

PMID:
28349199
PMCID:
PMC5508038
DOI:
10.1007/s00401-017-1703-0
[Indexed for MEDLINE]
Free PMC Article

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