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Science Alert: Experts Respond

Potential human transmission of Alzheimer’s – Expert reaction

Posted in Science Alert: Experts Respond on September 10th, 2015.

The medical fallout from a historic hormone treatment has revealed that the amyloid beta protein associated with Alzheimer‘s disease may be passed from one person to another, according to a new study. However, experts say the findings, while fascinating, do not represent a current health risk.

Vials and SyringeNew European research, published today in Nature, examined the post-mortem brain tissue of eight patients who contracted Creutzfeldt-Jakob disease (CJD) after receiving injections of human growth hormone extracted from human brain tissue.

The researchers identified molecular signs of Alzheimer‘s disease in four of the brains, suggesting that the contaminated injections also carried amyloid beta proteins that could ‘seed’ neurological changes similar Alzheimer‘s disease – if not cause the disease itself.

You can read more about the research on Scimex.org.

The medical treatment in question is no longer used, however an estimated 159 New Zealanders received the human-derived hormone in the 60s and 70s, and six developed CJD).

The Science Media Centre collected the following expert commentary. Feel free to use these quotes in your reporting. If you would like to interview a New Zealand expert, please contact the SMC (04 499 5476; smc@sciencemediacentre.co.nz).

Associate Prof Maurice Curtis, Deputy Director of the Human Brain Bank and Associate Professor, University of Auckland, comments:

“This is very interesting work that demonstrates higher than usual amyloid pathology in the brains of 4 out of 8 patients who had CJD as a result of receiving growth hormones earlier in life. The importance of this work is in raising the possibility that amyloid pathology might be seeded in the brain as opposed to being endogenously produced in the brain.

“This is not the first time the concept of transmissibility has been raised but usually the context relates to inhaling, ingesting or smelling a toxin that then begins the process of amyloid accumulation. To date both transmissibility and the toxin argument are unproven but remain tantalising hypotheses.

“The current study has been performed on a very small number of patients, and patients who received the growth hormones but did not get Creutzfeld Jacob disease do not appear to have been tested for amyloid deposition…this is a serious limitation in this study.

“The size of the study and the lack of direct evidence that the growth hormone injection led to amyloid deposition is a limiting factor in this study (no smoking gun). With that said, until we know exactly how degenerative brain diseases begin we must not exclude any possibilities.

“The work we are doing in my laboratory at the Centre for Brain Research is directly related to understanding the route of entry and early origins of degenerative diseases and so I can see the value in pursuing the line of research this group has taken.”

From the Australian Science Media Centre

Dr Claire Shepherd is a Senior Research Facility Manager at the Sydney Brain Bank and Conjoint Lecturer in Pathology, UNSW, comments:

“The findings are certainly interesting and warrant further investigation. Amyloid-beta protein deposition is an unusual finding in the brains of young individuals who do not have a known genetic predisposition to the disease.  The first question to answer is whether transmission through contaminated injections is in fact possible and can lead to full blown Alzheimer‘s disease (tau, amyloid-beta deposition and cell loss).

“The incubation period was extensive and progression of the disease would certainly be expected during this time if the normal disease process was underway. The diffuse amyloid-beta deposits seen would certainly not be sufficient to cause clinical Alzheimer‘s disease. Whilst further research is clearly warranted, it is premature to suggest that medical procedures involving implements that had previously been used on individuals affected with Alzheimer‘s disease could cause transmission of the disease.”

Professor Colin Masters is Senior Deputy Director of The Florey Institute and Laureate Professor at The University of Melbourne

“The numbers of cases are small (eight), but four of these did have significant amyloid beta deposition, so it comes down to an assessment of whether this is more than would be expected in an aged-matched population (ages 36-51). This age span is exactly at the transition period between normality and the earliest  phases of preclinical sporadic Alzheimer‘s disease. We were the first to explore this age group in 1988*. In our sample we did not find anyone positive under the age of 50 years, but only 20 cases were looked at. In the current study, the authors used a special technique (formic acid prion inactivation which incidentally retrieves antigens normally invisible) which may have enhanced their ability to see the amyloid beta plaques in this young age group.

“So we need to be very careful over the interpretation of these findings. Most importantly, there are many recipients of pituitary products from the past (approximately 2000 people in Australia received the product and 4 of them developed CJD), who will be concerned now whether they have an increased risk of developing AD. Our message to these recipients is that much more work is required to settle this issue. Currently, Prof Steve Collins of the Australian National CJD Case Registry is reviewing all the files of recipients who have died  over the last 30 years. This work is ongoing and we will get results in the near future.”

Dr Bryce Vissel is the Roth Fellow Head of Neurodegeneration Diseases Research Laboratory at the Garvan Institute of Medical Research.

“This extraordinary study by John Collinge, Sebastian Brandner and colleagues suggests that healthy individuals exposed to cadaver-derived Human growth hormone may be at risk of Alzheimer‘s disease, and the related cerebral amyloid angiopathy as well as iatrogenic  Creutzfeldt-Jakob disease as they age. This study is extraordinary as it suggests that pituitary glands of humans used to make the human growth hormone contained seeds that caused the amyloid beta pathology observed.

“This matters enormously as it raises the possibility that other routes of transmission, including surgical instrument use and blood transfusion, could be relevant to the transmission of Alzheimer‘s disease, cerebral amyloid angiopathy and other neurodegenerative diseases. There however continues to be great controversy around the mechanisms that cause Alzheimer‘s disease and so the current study will be yet another one that adds to the challenging and important ongoing debate.”

From the UK Science Media Centre

Prof David Allsop, Professor of Neuroscience, University of Lancaster, said:

“I can imagine that this might result in a lot of misleading headlines. What the paper shows is that some people treated with human growth hormone who subsequently went on to develop CJD also show evidence of ? amyloid deposits, a key feature of Alzheimer‘s disease, in their pituitary glands. What the paper does NOT demonstrate is whether these people would have gone on to develop Alzheimer‘s disease had they lived long enough (they died of CJD) or that their pancreatic ? amyloid deposits were caused by contamination of growth hormone with a ‘rogue’ form of ? amyloid. One possible (and indeed likely) explanation is that deposition of the ‘prion protein’ in CJD can result, in some cases, in the co-accumulation of ? amyloid.

“It is very well known from other studies that one type of rogue protein (in this case the prion protein) can predispose to accumulation of another (in this case ? amyloid). There is no evidence that Alzheimer‘s disease can be transmitted from one person to another, or through use of contaminated surgical instruments, and these results should be interpreted with a great deal of caution.”

Dr Doug Brown, Director of Research at Alzheimer‘s Society, said:

“While these findings are interesting and warrant further investigation, there are too many unknowns in this small, observational study of eight brains to draw any conclusions about whether Alzheimer‘s disease can be transmitted this way.

“Notably, while seven of the eight brains studied had beta-amyloid deposits – a protein found in the brains of people with Alzheimer‘s disease – the presence of this alone does not mean that they would have gone on to develop the disease.

“Injections of growth hormone taken from human brains were stopped in the 1980s. There remains absolutely no evidence that Alzheimer‘s disease is contagious or can be transmitted from person to person via any current medical procedures.”

Prof John Hardy, Professor of Neuroscience, UCL, said:

“Work largely from Germany over the last 5 years has shown that the amyloid pathology of Alzheimer‘s disease could be transmitted from mouse to mouse on injection of amyloid.  In the 1980s Creuzfeldt-Jacob (prion) disease was transmitted to a small percentage (~4%) of individuals who were given human brain derived growth factor. They developed this presumably because the injections contained infectious prion protein.

“This study reported today shows that about half of those patients (that is about 2% of the original cohort) also, unexpectedly, had amyloid pathology in addition to their prion pathology suggesting, perhaps, that the amyloid pathology also infected the injected humans.  We do not know the clinical outcome of the vast majority of those who received the growth factor injections but they did not get prion disease.

“What does this mean?  With the previous mouse data, I think we can be relatively sure that it is possible to transmit amyloid pathology by the injection of human tissues which contain the amyloid of Alzheimer‘s disease.  Does it have implications for (for example), blood transfusions: probably not, but this definitely deserves systematic epidemiological investigation.  Does it suggest Alzheimer‘s disease is infectious through contact?  Almost certainly not.”

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