Neurosurgery could spread protein linked to Alzheimer’s, study finds

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By Ian Sample Science editor

Doctors should decontaminate tools more thoroughly as a precaution, say researchers

Surgical instruments used in brain operations should be treated to ensure they are not contaminated with proteins linked to Alzheimer’s disease, according to scientists who found evidence that they may be spread by certain medical procedures.

The researchers urged doctors to decontaminate neurosurgical tools more thoroughly as a precautionary measure to reduce the potential risk of spreading abnormal proteins known to build up in the brains of Alzheimer’s patients.

Prof John Collinge, director of the Medical Research Council prion unit at University College London, said that while Alzheimer’s disease was not contagious, there was a slim risk that harmful proteins that drive the disease could spread through brain surgery and other rare procedures.

“We don’t know if any cases of Alzheimer’s disease are related to medical or surgical procedures, but in my view we should take a precautionary approach,” Collinge told reporters at a press briefing.

Alzheimer’s disease affects more than half a million people in Britain. The condition impairs memory and cognitive abilities and is characterised by the buildup of toxic protein deposits in the brain. So-called amyloid beta plaques form between nerve cells, while tau protein tangles form inside the nerve cells.

The UCL team investigated a small number of patients who died of Creutzfeldt-Jakob disease (CJD) in Britain after being treated with contaminated growth hormone taken from cadavers. The hormone was extracted from thousands of people’s pituitary glands, pooled together and injected into about 30,000 children, predominantly with stunted growth, between 1958 and 1985.

Most of the CJD patients also had a condition called cerebral amyloid angiopathy (CAA), a brain disorder related to Alzheimer’s disease. In CAA, amyloid plaques build up in the brain’s blood vessels, rather than between nerve cells, as happens in Alzheimer’s.

The researchers tracked down old vials of the CJD-contaminated hormone and tested them for precursors of amyloid and tau proteins. The only vials that tested positive contained hormones extracted by the particular method used for the British patients’ injections.

To test whether the contaminated hormone could spread disease, the scientists injected it directly into the brains of mice that had been genetically modified to enable them to make human amyloid beta proteins. The mice soon developed clumps of amyloid beta and cerebral amyloid angiopathy. The researchers believe that amyloid beta “seeds” that contaminated the hormone triggered the formation of plaques once injected into the brain.

While the mice did not develop Alzheimer’s disease, the study reported in Nature suggests that amyloid beta “seeds” could potentially be spread by certain medical procedures and may theoretically give rise to disease.

“With CAA and probably with Alzheimer’s disease there may be certain circumstances, though hopefully rare, that transmission of the pathology can occur,” said Collinge.Studies have found no evidence that Alzheimer’s disease can be spread by blood transfusions, but Collinge pointed out that many recipients of blood transfusions do not live long enough afterwards for dementia to develop.

“Transfusion is not a major risk for me, I’m more concerned about neurosurgical instruments,” he said. “I think it’s important we do further research on this and develop new ways to remove these seeds, so any risk that is there is removed,” he said.

“We ought to be doing epidemiological studies to see if there is any link between these medical procedures and Alzheimer’s disease. We can also think about better means to decontaminate surgical instruments to remove this risk. It’s a small risk, and a risk of something happening 20 years after exposure, but in my view you want to be doing research to remove that risk.

“No one should not have neurosurgery as a result of this,” Collinge added. “But if we can avoid any transmission of CAA or Alzheimer’s disease we should do it, even if it’s only a handful of people who are at risk.”

In an accompanying article, David Holtzman and Tien-Phat Huynh at Washington University in St Louis write: “It is crucial that surgical instruments that come into contact with the human brain are appropriately treated to remove seeds of misfolded forms of peptides and proteins.”

But Bart de Strooper, director of the UK Dementia Research Institute at UCL, who was not involved in the study, said: “It is possible that neurosurgical instruments could become contaminated with amyloid seeds, and likely with tau or one of the many other abnormally folded proteins that cause neurodegeneration such as alpha-synuclein in Parkinson’s disease.

“However, surgeons already take precautions to avoid contamination by prions and those should be sufficient to prevent also these types of contamination. There is absolutely no reason to postpone or decline brain surgery based on the current evidence.”

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