Transmission of amyloid-[beta] protein pathology from cadaveric pituitary growth hormone

• Published in: Nature (London) 2018-12, Vol.564 (7735), p.415
• Main Authors: Purro, Silvia A, Farrow, Mark A, Linehan, Jacqueline, Nazari, Tamsin, Thomas, David X, Chen, Zhicheng, Mengel, David
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-protein; Creutzfeldt-Jakob disease; Disease transmission; Health aspects; Hormones; Human development; Medical errors; Medical research; Peptides; Physiological aspects; Pituitary hormones; Proteins; Public health; Seeds; Somatotropin; Surgery
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-018-0790-y

We previously reported.sup.1 the presence of amyloid-[beta] protein (A[beta]) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitary-derived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular A[beta] in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzheimer's disease brain homogenates to seed A[beta] deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with A[beta] seeds as well as with prions. However, this was necessarily an association, and not an experimental, study in humans and causality could not be concluded. Given the public health importance of our hypothesis, we proceeded to identify and biochemically analyse archived vials of c-hGH. Here we show that certain c-hGH batches to which patients with iCJD and A[beta] pathology were exposed have substantial levels of A[beta].sub.40, A[beta].sub.42 and tau proteins, and that this material can seed the formation of A[beta] plaques and cerebral A[beta]-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of A[beta] seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of A[beta] pathology. This experimental confirmation has implications for both the prevention and the treatment of Alzheimer's disease, and should prompt a review of the risk of iatrogenic transmission of A[beta] seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission.sup.2,3.