Alzheimer's 'seeds' found in seven CJD victims' brains

The results of a study that reported finding markers for Alzheimer's disease in the brains of some people who died of Creutzfeldt-Jakob disease (CJD) has led to many inaccurate headlines in the press.

The Daily Mirror claims "You can catch Alzheimer's", while the Mail Online claims that an "explosive new study suggests the disease is spread like CJD and could be passed on through blood transfusions, operations and dental work".

Neither claim adds up to much scrutiny, as the "explosive" study itself concludes: "There is no suggestion that Alzheimer's disease is a contagious disease and no supportive evidence … that Alzheimer's disease is transmissible, notably by blood transfusion".

The eight people involved in the study were infected with brain-damaging proteins called prions, which cause CJD, through injections of human growth hormone taken from the brains of people who had died. All the infections happened before 1985, when this type of treatment was stopped.

None of the eight people studied actually had Alzheimer's – they all died of CJD. During their autopsies, researchers were surprised to find evidence of amyloid beta protein deposits (abnormal clumps of protein), which can be a precursor of Alzheimer's, in seven people's brains.

These people were aged 36 to 51 years – too young for most people to develop Alzheimer's. The researchers suggest they may have been infected with amyloid proteins – dubbed Alzheimer's "seeds" – in the same way they had been infected with prions: through human growth hormone treatment.

But nobody should worry that they have "caught" Alzheimer's from routine medical treatment using the information this study has gathered.

Where did the story come from?

The study was carried out by researchers from the National Hospital for Neurology and Neurosurgery, the Medical Research Council Prion Unit, and University College London, and was funded by the UK Medical Research Council and the National Institute of Health Research.

Two of the study authors are shareholders in a company called D-Gen. This is a company working in the field of prion disease diagnosis, decontamination and therapeutics.

This might be seen as a conflict of interest. This fact was not reported in the UK media though the potential conflict of interest was made clear by the authors themselves in the study.

The study was published as a letter in the peer-reviewed science journal Nature on an open-access basis, so anyone can read the study for free online.

The quality of the UK's media reporting was decidedly mixed. The actual reporting of the study was generally accurate and contained useful words of reassurance from independent experts.

For example, Dr Eric Karran, director of research at Alzheimer's Research UK, was quoted as saying: "There is currently no evidence to suggest that the amyloid protein could be passed through dental surgery or blood transfusions." Indeed, a study in 1997 found that Alzheimer's disease was more common in people who had not had blood transfusions.

But the headline writers had a field day, generating a range of needlessly alarmist and inaccurate headlines, from the Mirror's "You can catch Alzheimer's" and the Mail's "Alzheimer's links to blood transfusions", to the Daily Express' "Alzheimer's bombshell". 

What kind of research was this?

This autopsy study was part of a larger ongoing study looking into what happened to people in the UK who received human growth hormone therapy.

Researchers are trying to follow all the people who get CJD in the UK in a study called the National Prion Monitoring Cohort study and – where possible – perform autopsies after their death.

The aim is to advance our understanding of prion disease in the brain. The researchers were not expecting to find signs of Alzheimer's disease.  

What did the research involve?

Eight patients were given autopsies after they died of CJD following infection from human growth hormone. The researchers used standard techniques to look for prions in the brain and the damage they had done. They also looked for any other abnormalities.

The researchers reviewed autopsy results of 116 patients who had died from other types of prion disease so they could compare their initial results with groups of people with prion disease not caused by human growth hormone.

They also looked at the genetic profile of the eight people in their study to see if they had genetic mutations for early Alzheimer's.

Amyloid protein deposits are not common in the brains of younger people, unless they have a genetic mutation that means they are more likely to get early onset Alzheimer's. 

What were the basic results?

During the eight autopsies, the researchers found some evidence of amyloid protein deposits in seven of the patients. This was "substantial" in four patients.

They also found a build-up of amyloid protein in the brain arteries of four of the patients. Amyloid deposits in brain arteries can cause bleeding, strokes and dementia. None of the eight patients had genetic markers for early Alzheimer's.

The autopsy results of people who died from prion diseases not caught through medical treatment found none of them had similar results. Their results were in line with what you would expect to see in people across a similar age range. 

How did the researchers interpret the results?

The researchers concluded their findings were "consistent with the hypothesis that amyloid beta seeds have been iatrogenically [caused by medical treatment] transmitted to these patients with CJD". In other words, the patients were infected with amyloid proteins from the brain tissue used to make human growth hormone, in the same way they had been infected with prions.

They warned that, "amyloid beta seeds are known, like prions, to adhere to metal surfaces and to resist formaldehyde inactivation and conventional hospital sterilisation", and say scientists should consider whether amyloid protein could be transmitted through surgical instruments and blood products.  

Conclusion

This small study raises questions about how a group of relatively young people with CJD came to have amyloid protein deposits in their brains when they died. But it doesn't answer those questions.

The theory that amyloid proteins were transferred, along with prions, through growth hormone therapy is still just that: a theory. There are other possibilities – for example, the prions could have somehow encouraged the growth of amyloid protein. That would mean people who are already infected with prions are at an increased risk of early-onset Alzheimer's disease.

However, it's also important to remember no-one in the study actually developed Alzheimer's. They may have done so had they lived longer, but we don't know. As the cause of Alzheimer's remains unknown, it is also feasible that another process or risk factor could have accounted for the results seen.

Other studies that looked at people who received human growth hormone treatment found they were not at any increased risk of getting Alzheimer's disease. But that study only looked at death certificates, not autopsy results. We don't know if these people had amyloid protein deposits in their brains.

The implications if amyloid protein could be passed on through blood products and surgery are that many more people may be at risk of Alzheimer's than previously thought. Yet there is no evidence from this study to suggest this is the case. Previous studies looking at people who have had blood transfusions have not found they are more likely to get Alzheimer's disease.

This is just one small, exploratory study that made a surprising finding. Researchers will now need to look at other data – for example, any additional autopsy data from people who have died of CJD caused by medical treatment over the past few decades – to see whether these findings stand up.

NHS procedures have improved significantly since the 1970s, when the patients in this study contracted CJD. Modern surgical equipment used in the UK is very safe and the NHS has extremely stringent procedures to make sure of this. There has so far been no evidence of Alzheimer's disease being transmitted through surgery, blood transfusion or dental treatment.