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Potential brain disease risk posed by surgical procedures

Sticky proteins can be transferred between people

Jo Carlowe

Friday, 14 December 2018

Sticky proteins associated with neurodegenerative diseases can be transferred between people raising concerns over some surgical procedures.

The study* published this week in Nature showed that it is possible for the amyloid protein to transfer under particular conditions, and to cause damage in a recipient’s brain.

The researchers stress that their findings do not suggest that disorders such as Alzheimer’s disease are contagious, but it does raise concern that certain medical and surgical procedures pose a risk of transmitting such proteins between humans, which might lead to brain disease decades later.

“The risk may turn out to be minor — but it needs to be investigated urgently,” says John Collinge, a neurologist at University College London who led the research.

The work follows up on a provocative study published by Collinge’s team in 2015. The researchers discovered extensive deposits of a protein called amyloid-beta during post-mortem studies of the brains of four people in the United Kingdom. They had been treated for short stature during childhood with growth-hormone preparations derived from the pituitary glands of thousands of donors after death.

The recipients had died in middle-age of Creutzfeldt-Jakob disease (CJD), caused by the presence in some of the growth-hormone preparations of an infectious, misfolded protein — or prion — that causes CJD. But pathologists hadn’t expected to see the amyloid build up at such an early age. Collinge and his colleagues suggested that small amounts of amyloid-beta had also been transferred from the growth-hormone samples, and had caused, or ‘seeded’, the characteristic amyloid plaques.

Amyloid plaques in blood vessels in the brain are a hallmark cerebral amyloid angiopathy (CAA). In Alzheimer’s disease, however, amyloid plaques are usually accompanied by another protein called tau — and the researchers worry that this might also be transmitted in the same way. But this was not the case in the brains of the four affected CJD patients, which instead had the hallmarks of CAA.

The team has now more directly tested the hypothesis that these proteins could be transmitted between humans through contaminated biological preparations. Britain stopped the cadaver-derived growth hormone treatment in 1985 and replaced it with a treatment that uses synthetic growth hormone. But Collinge’s team located old batches of the growth-hormone from Porton Down.

When the researchers analysed the samples, their suspicions were confirmed: they found that some of the batches contained substantial levels of amyloid-beta and tau proteins.

To test whether the amyloid-beta in these batches could cause the amyloid pathology, they injected samples directly into the brains of young mice genetically engineered to be susceptible to amyloid pathology. By mid-life, the mice had developed extensive amyloid plaques and CAA. Control mice didn’t have amyloid build up.

The scientists are now checking in separate mouse experiments whether the same is true for the tau protein.

“It’s an important study, though the results are very expected,” says Mathias Jucker at the Hertie Institute for Clinical Brain Research in Tubingen, Germany. Jucker demonstrated in 2006 that amyloid-beta extracted from human brain could initiate CAA and plaques in the brains of mice. Many other mouse studies have also since confirmed this.

That the transmissibility of the amyloid-beta could be preserved after so many decades underlines the need for caution, says Jucker. The sticky amyloid clings tightly to materials used in surgical instruments, resisting standard decontamination methods. But Jucker also notes that, because degenerative diseases take a long time to develop, the danger of any transfer may be most relevant in the case of childhood surgery where instruments have also been used on old people.

So far, epidemiologists have not been able to assess whether a history of surgery increases the risk of developing a neurodegenerative disease in later life — because medical databases tend not to include this type of data.

But epidemiologist Roy Anderson at Imperial College London says researchers are taking the possibility seriously. Major population cohort studies, such as the US Framingham Heart Study, are starting to collect information about participants’ past surgical procedures, along with other medical data.

Commenting on the findings, Dr James Pickett, head of research at Alzheimer’s Society, said: “This is a scientifically robust study, which shows a small number of people that had this rare growth hormone replacement procedure decades ago likely had the amyloid protein transferred to them. We’ve known for a long time that amyloid protein is involved in Alzheimer’s disease, but it is just one component.

“Although researchers found that some of the people who received this procedure had changes in their brain related to the amyloid protein, they didn’t have Alzheimer’s disease itself. The procedure in this study was phased out over 35 years ago, and more modern approaches do not have the same risk of exposure.

“There remains absolutely no evidence that Alzheimer’s disease is contagious. There are no examples of Alzheimer’s being transmitted from person to person via any current surgical procedures and there is good evidence to show that blood transfusions don’t increase your chances of developing Alzheimer’s disease.”

*Purro SA, Farrow MA, Linehan J, et al. Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone. Nature, 13 December 2018, DOI:10.1038/s41586-018-0790-y

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