‘Seeds’ of Alzheimer’s might be transferred on medical instruments

Seeds of Alzheimer’s disease can potentially attach to surgical instruments and be transferred from one person to another during certain medical procedures, a study suggests.

The findings provide the first evidence of dementia transmission in humans via microscopic protein fragments.

Health officials and experts were quick to reassure the public after the highly controversial research was reported in the leading journal Nature.

However the findings prompted speculation about the safety of some medical procedures, including dental treatments. Blood donations are not considered a meaningful risk, but should be investigated as a precaution, say the researchers.

British scientists stumbled on the discovery while investigating a rare form of “iatrogenic” Creutzfeldt Jakob Disease (iCJD), a brain-destroying condition known to be spread by contaminated surgical instruments and procedures.

They inspected the brains of eight patients who died from the disease after receiving pituitary growth hormone extracted from cadavers.

Unexpectedly, six bore a clear molecular hallmark of Alzheimer’s – sticky clumps of fragmented protein called amyloid beta that form among neurons and on the walls of blood vessels. In four cases, the amyloid deposits were widespread and only one patient was not affected at all.

All eight individuals were relatively young, aged 36 to 51, and none had genetic variants associated with early-onset Alzheimer’s disease.

The evidence points to the hormone carrying “seeds” of the Alzheimer’s protein into the patients’ brains as well as CJD.

Since the prion proteins responsible for iCJD can be transmitted in other ways – for instance, by neurosurgery – experts are not ruling out the possibility that the same is true for the Alzheimer’s molecule.

Lead scientist Professor John Collinge, director of the Medical Research Council Prion Unit at University College London, said there was increasing evidence that neurodegenerative diseases including Alzheimer’s might, in rare circumstances, be “acquired”.

Speaking on a phone-link to the British Science Festival taking place at the University of Bradford, he said: “You could have three different ways you have these protein seeds generated in your brain. Either they happen spontaneously, an unlucky event as you age, or you have got a faulty gene, or you’ve been exposed to a medical accident. That’s what we’re hypothesising.”

He pointed out that, like CJD prions, amyloid beta protein fragments stick to metal surfaces and resist conventional sterilisation.

Previous experiments on laboratory mice and monkeys had already shown that transmission of the Alzheimer’s protein is theoretically possible.

When liquified brain tissue from dead Alzheimer’s patients was injected into the central nervous systems of the animals, they developed the brain changes associated with the disease.

The scientists do not believe CJD prions somehow triggered the development of amyloid beta deposits in the brains of the growth hormone patients. Brains of 116 patients with prion diseases who had not received pituitary growth hormone did not have the Alzheimer’s hallmark, and the two diseases affect different brain areas.

Other research has shown that amyloid beta can form in the pituitary gland, a pea-sized body at the base of the brain.

None of the patients had developed Alzheimer’s symptoms and their brains did not show another key change associated with the disease, twisted strands of protein within nerve cells called tau tangles. Whether or not they would have started to suffer symptoms had they lived longer remains an unanswered question.

Questioned specifically about dentistry, Prof Collinge said: “The seeds will potentially stick to metal surfaces whatever the instrument is. With prions, we know quite a lot about that. Certainly, there are potential risks with dentistry where it’s impacting on nervous tissue, for example root canal treatment, and special precautions are taken with reamers that are used in root canal treatment for that reason, in the UK at least.

“If you are speculating that amyloid beta seeds might be transferred by instruments, one would have to consider whether certain types of dental procedure might be relevant.”

He stressed there was no epidemiological evidence at all to suggest that Alzheimer’s could be transmitted via blood transfusions, but added: “I think it’s not unreasonable to have a look. My concerns would be more to see if there is a risk of seeding from metal surfaces. I think that is something we ought to prioritise.”

Later he appeared to backtrack on dental treatments, issuing a statement saying the current data had “no bearing” on dental surgery and “certainly do not argue that dentistry poses a risk of Alzheimer’s disease”.

Prof Collinge said: “Our findings relate to the specific circumstance of cadaver-derived human growth hormone injections, a treatment that was discontinued many years ago. It is possible our findings might be relevant to some other medical or surgical procedures, but evaluating what risk, if any, there might be requires much further research.”

Meanwhile, he urged people not to be concerned about planned medical procedures, and to dismiss any notion of Alzheimer’s being “contagious” in the same way as flu, for instance.

“No way is this suggesting that Alzheimer’s is a contagious disease,” he said. “You can’t catch it by living with someone who has Alzheimer’s disease or being a carer.

“I don’t want to cause any alarm. No-one should consider cancelling or delaying any kind of surgery. But I think it would be prudent to do some research in this area going forward.”

The chief medical officer, Professor Dame Sally Davies, also stepped in to reassure the public, maintaining there was “no evidence” that Alzheimer’s disease can be transmitted in humans through any medical procedure.

She added: “This was a small study on only eight samples. We monitor research closely and there is a large research programme in place to help us understand and respond to the challenges of Alzheimer’s.

“I can reassure people that the NHS has extremely stringent procedures in place to minimise infection risk from surgical equipment, and patients are very well protected.”

Treatment of people of short stature with pituitary growth hormone taken from dead donors began in the UK in 1958. It was stopped in 1985 after confirmed reports of CJD among recipients.

Because growth hormone from different cadavers was mixed up before being distributed, a treatment given to an individual patient may have originated from a large number of donors. This greatly increased the risk of disease transmission.

In total, 1,848 men and women in the UK underwent the procedure for stunted growth, and of these 77 have so far died from CJD.

As of 2012, 450 cases of iatrogenic CJD have been identified around the world linked to cadaver-derived growth hormone and to a lesser extent other medical procedures, including corneal transplants and neurosurgery.

The fear is that Alzheimer’s protein seeds could follow similar transmission pathways as CJD prions.

Dr Eric Karran, chief scientist at the charity Alzheimer’s Research UK, said: “The biggest risk factor for Alzheimer’s is age, along with genetic and lifestyle factors. If further research was to confirm a link between historical tissue contamination and Alzheimer’s, it would only likely be relevant to a tiny proportion of the total number of people affected.”

Dr Doug Brown, director of research at Alzheimer’s Society, said: “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.”

Professor Nigel Hunt, dean of the faculty of dental surgery at the Royal College of Surgeons, said: “This study alone does not provide any conclusive proof that Alzheimer’s disease can be transmitted from person to person. Dental practice carries no more risk than any invasive clinical procedure. This is new research in a field of relatively recent scientific enquiry that needs to be taken seriously with further research to inform any changes to all clinical and dental practice.

“In dentistry, patients are protected from infection risks through the widespread use of single use instruments. All dental instruments that are reused are covered either by guidance from Nice (National Institute of Health and Care Excellence) or guidance about decontamination in primary care dental practices. The findings from today’s study must be considered by all relevant organisations to ensure current guidance is as robust as it needs to be.”

The British Dental Association’s scientific adviser, Professor Damien Walmsley, said: “Dentists take patient safety very seriously and follow strict protocols to protect patients from the risk of infections, however slight that risk may be.

“These protocols were strengthened in 2007 when a UK-wide restriction on the re-use of files that come into contact with nervous tissue during root canal treatments was put in place.

“These measures make dentistry one of the safest areas of healthcare.”

Q & A

Q: What has been discovered?

A: The first clinical evidence that “seeds” of brain abnormalities closely associated with Alzheimer’s disease can be transmitted between people. Alzheimer’s patients have clumps of sticky material made from protein fragments, called beta amyloid, in their brains. Similar deposits can build up on the walls of blood vessels in the brain. The new evidence raises the possibility that microscopic amyloid particles can pass from person to person as a result of medical procedures.

Q: How was the discovery made?

A: Scientists led by Professor John Collinge, from the Medical Research Council Prion Unit in London, were examining the brains of eight individuals who had died from Creutzfeldt Jakob Disease (CJD), a rare and lethal brain condition, after receiving pituitary growth hormone to treat stunted growth. The hormone, produced by the pituitary gland, a pea-sized organ at the base of the brain, was taken from the brains of dead donors. Unexpectedly, as well as the damage caused by CJD, the researchers also found clear signs of the beta amyloid Alzheimer’s hallmark in six of the patients. In four the deposits were widespread, and only one patient was completely amyloid free.

Q: What does this mean?

A: How did the beta amyloid get there? The eight patients were aged 36 to 51, very young to show clinical signs of Alzheimer’s. None had genetic variants associated with early-onset Alzheimer’s. After careful investigation the scientists concluded the most likely explanation was that “seeds” of beta amyloid were passed to the patients in the growth hormone they were treated with. There is no evidence that having CJD could somehow trigger Alzheimer’s, which affects different parts of the brain.

Q: Why the concern?

A: There is growing evidence that in rare circumstances it might be possible to “acquire” Alzheimer’s, or at least the brain changes associated with it. In animal tests, mice and monkeys injected with liquified brain material from dead Alzheimer’s patients have gone on to develop beta amyloid deposits in their brains. But this has never been shown to occur in humans before.

Q: Does this mean you can catch Alzheimer’s?

A: No, not in the sense that you can catch a cold. Alzheimer’s is definitely not contagious. But the possibility cannot be ruled out that brain changes associated with the disease can be triggered by seeds spread by some medical procedures.

Q: Did the growth hormone patients have Alzheimer’s?

A: They did not. But most had a pathology – a physical symptom – linked to the disease. Whether or not they would have gone on to develop Alzheimer’s had they lived longer remains an unanswered question.

Q: Could going to the dentist put you at risk?

A: Almost certainly not. But beta amyloid particles are known to stick to metal, and are hard to remove even by normal sterilisation procedures. That means they could conceivably stick to surgical instruments, including the tooth probes used by dentists. This might be relevant to procedures that come in to contact with nerves, like root canal treatments, say the scientists. However, the likelihood of Alzheimer’s amyloid being transmitted in this way is extremely remote.

Q: What is the connection with CJD?

A: CJD is thought to be transmitted by wrongly-shaped rogue proteins, called prions. There are three main categories of CJD – spontaneous, which occurs simply by bad luck with age, familial, which is due to inherited genes, and acquired, which is transmitted in some way. Acquired CJD includes the subtype “iatrogenic” CJD (iCJD) which is transmitted through surgical procedures, and “variant” CJD, which first appeared in 1996 and is caused by eating prion-contaminated beef. Prof Collinge and other experts are now beginning to think that Alzheimer’s and possibly other neurodegenerative diseases like Parkinson’s might follow a similar pattern. Some cases might be sporadic, others familial, and others acquired. In the case of Alzheimer’s, the transmissible agent would not be a prion but a beta amyloid particle, or “seed”. Both prions and beta amyloid particles are hard to remove from metal surfaces.

A number of procedures have been known to transmit iatrogenic CJD. They include neurosurgery, corneal transplants, the placing of electrodes into the brain, and the use of grafts of dura mater, a membranous sac surrounding the brain. Similar routes of transmission may conceivably apply to beta amyloid seeds.

Q: Is growth hormone treatment still dangerous?

A: People in the UK were treated with pituitary growth hormone extracted from cadaver brains from 1958 to 1985. This was stopped when it was realised a high proportion of patients were contracting CJD. In total 1,848 men and women were treated with pituitary growth hormone, of whom 77 have died from the disease. Today a safe form of synthetic growth hormone is used to treat stunted growth.

Copyright (c) Press Association Ltd. 2015, All Rights Reserved.