January 29, 2024

expert reaction to study of Alzheimer’s Disease in recipients of cadaveric pituitary-derived growth hormone

A study published in Nature Medicine looks at Alzheimer’s Disease in recipients of cadaveric pituitary-derived growth hormone.

Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said:   

“This study provides evidence of an extremely rare and unusual route through which Alzheimer’s disease could potentially have been transmitted to some patients after they received human growth hormone from deceased donors’ brains. However, it is not known how common Alzheimer’s transmission was in the 1,800 people who had this treatment and the study only looked at the records of eight people.  

“With the treatment not used since 1985, there is no cause for concern for the health of the general population. Nowadays, patients receive synthetic alternatives which have been approved for safety and do not pose a risk of transmitting diseases.  

“There are no safety concerns with today’s treatments as they were developed to minimise the risk of any transmissible diseases. Crucially, there is also no evidence that Alzheimer’s disease can be transmitted in the context of daily life activities, or routine care.  

“If you have concerns about yourself or a loved one, Alzheimer’s Society is here to provide advice and support. Our free symptoms checklist can be accessed via our website at alzheimers.org.uk.”    

Dr. Maëva May, Associate Director of Research at the Stroke Association said:

“Each year, 100,000 people in the UK have a stroke. Even for those who survive, it is a catastrophic event. Many are left unable to talk, walk, and need support to rebuild their lives.

“When we started funding Dr Banerjee, Stroke Association was eager to find out what her work could tell us about the risk of stroke in people who’ve received dura mater (the membrane covering the brain) or growth hormones from deceased donors. We’re very pleased that her work is also bringing benefits to our understanding of dementia and has the potential to help us find shared treatments for Alzheimer’s disease and certain types of bleeding stroke.

“More than 30 years ago, we learned that the people who received growth hormones from deceased donors – who were mainly children at the time they received it – were at increased risk of developing Creutzfeldt-Jakob disease (CJD). In light of this, the treatment was banned.

“Later studies revealed that those who’d had dura mater transplants were at increased risk of haemorrhagic (bleeding) strokes in their 30s and 40s due to cerebral amyloid angiopathy (CAA), which is a build-up of amyloid beta protein in the blood vessels. CAA is largely a disease of older adulthood, but these patients were developing it decades earlier than we’d usually expect. Given that the same protein is often present in growth hormone from deceased donors, it seemed likely that people who’d received it would also be at risk of CAA-related strokes.

“This new study has shown that those who received growth hormones are instead at risk of early onset Alzheimer’s disease as the amyloid beta protein is building up in the brain tissue as well as the blood vessels. We don’t yet understand why exposure to the same protein carries different risks for different people and we eagerly await further developments that could help unravel this mystery.

“The participants in this study are necessarily a very small group of people – under 2,000 people in the UK ever received growth hormone from deceased donors and research in this area currently relies on volunteers coming forward. However, this work has implications for Alzheimer’s disease and CAA in the general population, and we’re excited about the potential of this research to help us find shared treatments for these conditions.

“We’re proud to be working with Alzheimer’s Research UK and the NIHR to fund Dr Banerjee in the next stages of her work.

“We also want to reassure people learning about this research that they are not at risk of catching stroke or Alzheimer’s disease from touching a stroke survivor or someone living with dementia; the risk of catching either is tied to specific medical treatments that are no longer practiced. It is also extremely unlikely that you would be unaware if you had received growth hormones from a deceased donor; recipients and their families were notified by the government in the mid-1990s after the link to CJD was discovered.

“The people who’ve received these treatments have already been through so much: the initial condition that led to the treatment, the risk of CJD, the risk of bleeding strokes, and now the risk of early-onset Alzheimer’s disease.”

Dr Susan Kohlhaas, Executive Director of Research and Partnerships at Alzheimer’s Research UK said:

“A diagnosis of Alzheimer’s disease can be devastating for all involved, and our hearts go out to the families that have been affected by these tragic circumstances.

“This study suggests that in very rare circumstances Alzheimer’s disease may be transmitted between humans via human growth hormone from deceased donors. It must be stressed that this treatment is no longer used today and has been replaced with synthetic growth hormone.

“Researchers found that the growth hormone had the potential to contain fragments of amyloid, and a small number of people treated with this went on to develop symptoms of Alzheimer’s disease. Other potential causes of cognitive impairment, such as genes linked to young-onset Alzheimer’s, and whether having a growth hormone deficiency itself was linked to Alzheimer’s development, were also ruled out.

“After human growth hormones were no longer used in the 1980s due to concerns over Creutzfeldt-Jakob disease transmission, strict procedures were put in place to minimise cross-contamination. But in light of these findings, researchers recommend that medical procedures should be reviewed to ensure that rare cases of Alzheimer’s transmission like this do not happen in the future.

“It’s also important to stress that this is the only recorded instance of Alzheimer’s transmission between humans. There is no evidence to suggest that it can be passed through any other route, such as day-to-day activities or routine medical procedures. But this study has revealed more about how amyloid fragments can spread within the brain, providing further clues on how Alzheimer’s disease progresses and potential new targets for the treatments of tomorrow.

“At Alzheimer’s Research UK, we will continue to redouble our research efforts in our pursuit for a cure.”

Prof Bart De Strooper, Group Leader at the UK Dementia Research Institute at UCL, said:

“This is a very interesting study providing further insight on the risk of a transmissible form of amyloid beta, a protein implicated in cerebral amyloid angiopathy and Alzheimer’s disease. 

“As the authors noted, based on current evidence, the risk of acquiring a transmissible form of amyloid is very low. No one should reconsider or forego any medical procedure, especially for blood transfusion or neurosurgery which saves many lives worldwide every year. 

“However, it is always important that we continue to review and scrutinise evidence where public health is concerned. In previous correspondence involving several experts in the field (see reference), we have called for increased vigilance and long-term monitoring, particularly following procedures in early life that involve human fluids or tissues. Practical steps recommended include conducting larger epidemiological studies, continued investigation of risk using animal models, and the development of low cost, high-throughput sensitive tests for amyloid beta and other proteins to facilitate the precautionary sterilisation of, for example, neurosurgical instruments.” 

Reference: Potential human transmission of amyloid β pathology: surveillance and risks. Lancet Neurol. 2020 Oct;19(10):872-878. doi: 10.1016/S1474-4422(20)30238-6. Epub 2020 Sep 16.

Prof Tara Spires-Jones, Group Leader in the UK Dementia Research Institute and President of the British Neuroscience Association, said:

“This study looked at whether people can develop Alzheimer’s disease as a result of a growth hormone treatment that is no longer used. As the authors of this study mention, there is no suggestion that Alzheimer’s pathology can be transmitted between individuals in activities of daily life. There is also no evidence that would provoke worry about current surgical procedures carrying any risk of transmitting Alzheimer’s disease. This current paper is a description of 8 people who received several years of injection of growth hormone extracted from human cadavers during childhood, 5 of whom went on to develop dementia 30-40 years later.  The scientists attribute these symptoms to possible transmission of Alzheimer’s-related amyloid pathology from the growth hormone that started clumping of this amyloid in the brains of these people.  While this is possible based on this paper and their previous data, it is not something for people to worry about as that type of growth hormone treatment is no longer used and even in people treated with that growth hormone, this outcome is very rare.  Further, it is not possible to know for sure whether these people developed dementia due to their growth hormone treatment for several reasons: this study only looked at 8 people (a very small sample size), several of the people also had other risks for dementia like intellectual disability (in 2 cases) or a gene that substantially increase risk of Alzheimer’s (1 case), and the pathology shown in the paper for the people who donate post-mortem brain tissue is much milder than is found in people who died from Alzheimer’s disease.”

Prof Andrew Doig, Professor of Biochemistry and Programme Director for Biochemistry, University of Manchester, said:

Does the press release accurately reflect the science?

“Generally, yes. However these final conclusions, based on the abstract, are very speculative: “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.”

“There is no evidence that the mode of disease transmission presented here (transmission by) has ever occurred elsewhere. We are already very careful about transmitting brain tissue between people, due to the small but real risk of passing on prions which might cause CJD.

“There is evidence that amyloid-beta aggregates can travel across synapses in the brain, spreading dementia. This work adds support to this idea. Whether the work has any implications for therapeutic strategies remains to be seen. The paper speculates on whether different strains of amyloid-beta are present, resulting from different aggregate structures, but present no direct evidence for this.

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes, the work is thorough and carefully done. As discussed above, the discussion on the need for new procedures, the existence of strains and implications for therapies are speculative and lack evidence. Otherwise, the conclusions are reasonable, but we must bear in mind that only 8 patients are considered.

How does this work fit with the existing evidence?

“Previous work has shown that aggregates of amyloid-beta could be transmitted to humans along with human growth hormone, though we did not know whether they had any effects. This new work suggests for the first time that these aggregates can indeed cause a disease resembling Alzheimer’s.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“It is well known that early onset Alzheimer’s can be caused by mutations in the PSEN1, PSEN2 or APP genes. This does not seem to be the case here. Other possible explanations for the Alzheimer’s symptoms are intellectual disability in the patients, other linked diseases, growth hormone deficiency or effects of radiotherapy. All were ruled out, leaving Alzheimer’s transmission from the growth hormone treatment as the best explanation for the disease symptoms. One must be cautious, however, as only 8 patients are considered and some data for them in incomplete, such as the genetics.

“It is important to emphasise, however, that these symptoms seem to have arisen from a medical procedure that was last used in 1982.

What are the implications in the real world?  Is there any overspeculation? 

“While the new type of Alzheimer’s reported here is of great scientific interest, as it reveals a new way to spread the disease, there is no reason to fear it, as the way in which the disease was caused was stopped over 40 years ago. Disease transmission from human brain to brain in this way should never happen again.”

‘Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth  hormone’ by Gargi Banerjee et al. was published in Nature Medicine at 16:00 UK time on Monday 29^th January.

DOI: 10.1038/s41591-023-02729-2

Declared interests

Dr Susan Kohlhaas: Alzheimer’s Research UK is one of the funders of this research

Prof Bart De Strooper: Not involved in this study

Prof Tara Spires-Jones: I have no conflicts with this study.

Prof Andrew Doig: I am a director, founder and consultant for PharmaKure, working on new diagnostics and therapeutics for Alzheimer’s Disease. I have no direct conflict of interest with this research.