In the news today, we’re hearing about a UK research study that has suggested the hallmark Alzheimer’s protein, amyloid, could have been passed between people in historic treatments with human-derived growth hormone in the 60s and 70s. This is one of the first suggestions that amyloid could pass between humans in a similar way to the prion protein responsible for Creutzfeldt-Jakob disease (CJD). In this blog, we’ll get to grips with the findings and what they might mean.
What did the study show?
Researchers based at the National Hospital for Neurology and Neurosurgery at Queen Square in London, University College London and the MRC Prion and Clinical Trials Units have been studying people who received human-derived growth hormone taken from deceased people between 1958 and 1985.
It’s not possible to know whether the amyloid in their brains would have caused them to develop Alzheimer’s too.
Around 1,800 people in the UK received this hormone, often used to treat children with stunted growth. However, around 4% of people in the UK who’d received the injections went onto develop CJD. This was still only 65 people, but more than you’d expect considering only around 1 in every million people in the population develop CJD each year. Researchers at the time concluded that some of the donations had been contaminated with the prion protein responsible for causing the fatal neurodegenerative disease. In response, the use of human-derived growth hormone was stopped and replaced with a synthetic form in 1985.
When the team followed-up eight patients who’d developed CJD as a result of a historic hormone injection, they found that four of them, aged between 36 and 51, also showed unusually high levels of the amyloid protein in the brain after death. Amyloid is one of two hallmark proteins that build up in the brain in Alzheimer’s.
When the team compared this to 116 brain samples from people who developed CJD for other reasons, they didn’t see such high levels of the hallmark protein. This suggested it may have been passed between people through contamination of the human-derived hormone, in a similar way to the prion protein which caused their CJD.
What does this mean for Alzheimer’s?
Because the eight people studied in this research died of CJD at a relatively young age, it’s not possible to know whether the amyloid in their brains would have caused them to develop the Alzheimer’s too.
A 2013 study looked for increased rates of Alzheimer’s and Parkinson’s in 6,190 people who had received human-derived growth hormone worldwide. Almost 800 of those people had died but none had Alzheimer’s or Parkinson’s disease registered on their death certificates. This is not a definitive conclusion, but is the only follow-up of people who received the injections before 1985 and doesn’t suggest a higher risk of either disease.
Prion protein and amyloid protein
The prion protein is found normally in cells but, in very rare situations, it clumps together abnormally to cause diseases like CJD in humans, or BSE in cattle (also known as ‘mad cow disease’). These diseases are thought to develop when an abnormally-folded prion protein triggers a healthy one to become abnormal, kicking off a chain reaction that causes a large build-up of abnormal prion protein inside nerve cells. Abnormal prion protein can be passed from human to human or animal to human through contaminated tissue, although not through the air or by direct contact.
This isn’t the first time researchers have studied similarities between the prion protein and proteins linked to diseases like Alzheimer’s. Research in animals has shown that amyloid may spread from nerve cell to nerve cell in a manner similar to abnormal prion protein.
Scientists have also shown it’s possible to inject amyloid from human or mouse brain into mice made genetically susceptible to the disease, and trigger that amyloid to spread and build-up in a similar way to what we see in Alzheimer’s. Today’s research provides some early evidence that the amyloid protein may be passed between humans in a similar way to the prion protein, although we don’t know whether that would have caused Alzheimer’s disease itself to develop.
Should we be concerned?
The prion protein is known to be sticky and resistant to conventional cleaning techniques. The majority of cases of CJD caused by treatments or procedures contaminated with the prion protein have come from human-derived growth hormone injections prior to 1985, with a very small number reported after historical brain surgery. A very small number of cases (four in the UK) of CJD were previously been reported due to abnormal prion protein thought to be passed in contaminated blood given via blood transfusion many years ago.
The biggest risk factor for Alzheimer’s disease is age, along with genetics and lifestyle.
Although today’s research suggests the amyloid protein may have also been passed in contaminated growth hormone injections, there is currently no direct evidence amyloid could also be passed via these alternative routes, or through dentistry (as some media coverage is suggesting). A small number of studies have previously found no link between blood transfusions and an increased risk of Alzheimer’s.
The biggest risk factor for Alzheimer’s is age, along with genetics and lifestyle. If a small number of historical surgical procedures were shown to be linked to the transmission of amyloid, it would only be likely to be relevant to a very small number of people and long-term implications of that are still unclear.
However, in light of today’s results, this is an area that is definitely due more research. Researchers will now also need to study whether proteins involved in other dementias such as dementia with Lewy bodies or frontotemporal dementia, could pass between people in a similar way.
What precautions are already in place?
We’ve known the risks of transmission of CJD for many years and steps have been put in place in the health service to minimise any contamination with prion protein. This should also have the same effect for reducing any possible risk of contamination with the amyloid protein too.
From 1985, the use of human-derived growth hormone stopped and was replaced with a synthetic version, and the NHS uses stringent procedures to minimise any risk of contamination through surgical equipment. There have been no reported cases of CJD caused through contaminated surgical procedures in the UK for decades.