Five people in the UK who were given growth hormones sourced from deceased people during childhood (which is now banned) developed early-onset Alzheimer’s disease, according to UK scientists. The findings suggest that Alzheimer’s disease may have medically acquired forms, they say, although there’s no evidence that it can be transmitted through routine care or daily life. Between 1959 and 1985, nearly 2,000 UK patients were treated with human growth hormone extracted from cadaver-sourced pituitary glands (c-hGH). Some developed Creutzfeldt–Jakob disease (CJD), linked with ‘mad cow disease’, so the practice stopped, and some of those patients had signs of Alzheimer’s in their brains. The study discusses eight patients given the hormone who did not develop CJD, five of whom developed early-onset dementia. The authors say this emphasises the need for measures to prevent any accidental transmission via medical treatments and procedures.
Journal/conference: Nature Medicine
Link to research (DOI): 10.1038/s41591-023-02729-2
Organisation/s: University College London (UCL), UK
Funder: The MRC Prion Unit
is core funded by the UK Medical Research Council. The clinical
research activities of the National Prion Clinic are supported by
the National Institute of Health Research (NIHR) UCLH Biomedical
Research Centre. G.B. is an NIHR Clinical Lecturer. We also
acknowledge research support from Alzheimer’s Research UK and
the Stroke Association. S.M. and J.C. are NIHR Senior Investigators.
Relevant grant numbers are as follows: ARUK-CRF2020A-003
(G.B.); SA L-MP 20\100002 (G.B.); NF-SI-0617-10175 (S.M.) and
From: Springer Nature
Evidence of transmissible Alzheimer’s disease in recipients of pituitary-derived growth hormone
Five people who received treatment with cadaver-sourced human pituitary-derived growth hormone during childhood (an approach now banned) developed early and progressive disturbances in cognition that met diagnostic criteria for Alzheimer’s disease. Although this outcome is very rare, these findings, published in Nature Medicine, suggest that Alzheimer’s disease may have medically acquired (iatrogenic) forms. However, there is no evidence that it can be transmitted in other contexts, such as routine care or daily life.
Between 1959 and 1985, at least 1,848 patients were treated with human growth hormone extracted from cadaver-sourced pituitary glands (c-hGH) in the United Kingdom. This product was withdrawn around the world after some of these people received prion-contaminated c-hGH and subsequently died of Creutzfeldt–Jakob disease (CJD). Post-mortem analyses previously revealed amyloid-beta pathology, a hallmark of Alzheimer’s disease, in the brains of some of these people. However, it is unclear if these people had symptoms of Alzheimer’s disease before their death, as it would have been masked by their CJD symptoms. Previous research showed that some archived batches of c-hGH still contained measurable quantities of amyloid-beta, and can transmit this pathology to mice.
In this current study, John Collinge and colleagues describe eight people from the United Kingdom who had received c-hGH as children but did not go on to develop CJD. Five of these patients displayed symptoms consistent with early-onset dementia (38–55 years of age at symptom onset) that met the diagnostic criteria for Alzheimer’s disease, with progressive impairment in two or more cognitive domains severe enough to affect the performance of their usual activities of daily living. Of the remaining three people, one had symptoms (onset at 42 years of age) that met the diagnostic criteria for mild cognitive impairment, another had subjective cognitive symptoms only, and the third was asymptomatic.
Biomarker analyses, which cannot be used to diagnose the disease in the absence of symptoms, supported the diagnosis of Alzheimer’s disease in two of the people diagnosed with the condition, and was suggestive of Alzheimer’s disease in one other person. The authors also conducted autopsy studies in two patients who died during the study period, including extensive brain tissue sampling; one of these patients also showed Alzheimer’s pathology. In addition, genetic testing for causative genes for early-onset Alzheimer’s was negative in the five patients for whom samples were available. The authors suggest that their findings indicate that Alzheimer’s disease is potentially transmissible, and propose that, similar to CJD, Alzheimer’s disease may have sporadic, inherited and rare acquired forms.
The authors indicate that iatrogenic transmission of Alzheimer’s disease is likely to be rare, as c-hGH is no longer used and the patients described in this study developed symptoms after repeated exposure over several years. However, they note that the recognition of amyloid-beta transmission emphasizes the need to review measures to prevent accidental transmission via other medical treatments and procedures. These findings could have implications for the processes that drive other types of Alzheimer’s disease and may provide insights into therapeutic strategies, they conclude.
Please note that an online press briefing for the paper below will take place UNDER STRICT EMBARGO on Thursday 25th January at 3 pm London time (GMT) / 10 am US Eastern Time.
Authors John Collinge and Gargi Banerjee will discuss the research. This will be followed by a Q&A session.
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