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Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone
Open accessAbstract
We previously reported 1 the presence of amyloid-β protein (Aβ) 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 Aβ 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 Aβ deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with Aβ 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 Aβ pathology were exposed have substantial levels of Aβ 40, Aβ 42 and tau proteins, and that this material can seed the formation of Aβ plaques and cerebral Aβ-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of Aβ seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of Aβ 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 Aβ seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission 2,3.
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“Therefore, PD might be one of many neurological disorders involving prion protein aggregation and propagation [81].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [81]
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“There is strong evidence that human-to-human transmission of amyloid pathology is possible.”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Purro et al., 2018
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Metadata
- Authors
- Purro, S. A., Farrow, M. A., Linehan, J., Nazari, T., Thomas, D. X., Chen, Z., Mengel, D., Saito, T., Saido, T., Rudge, P., Brandner, S., Walsh, D. M., & Collinge, J.
- Affiliations
- MRC Prion Unit (GB)
- Brigham and Women's Hospital (US)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Collinge, John
- ORCID
- Venue
- Nature
- Published
- 2018-12
- Volume
- 564
- Issue
- 7736
- Pages
- 415-419
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6708408
- OpenAlex
- W2905542822
- Cited by
- 191
- References
- 33
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 29 · 2023: 17 · 2022: 22 · 2021: 22 · 2020: 34 · 2019: 33 · 2018: 3
- FWCI
- 15.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council (MR/L022656/1)
- National Institute on Aging (R01AG046275)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- amyloid-beta, iatrogenic Creutzfeldt-Jakob disease, prion transmission, Alzheimer's disease, tau protein, iatrogenic transmission
- MeSH terms
- Alzheimer Disease, Animals, Cadaver, Disease Models, Animal, Drug Contamination, Female, Humans, Iatrogenic Disease, Creutzfeldt-Jakob Syndrome, Male, Models, Biological, Prions, Recombinant Proteins, Growth Hormone, Reproducibility of Results, Case-Control Studies, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Disease Transmission, Infectious, Mice
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