Alzheimer’s protein may be spread during surgery

A new study suggests that the precursor of an abnormal protein that triggers Alzheimer’s disease could perhaps be transmitted from person to person through the transfer of tissue or certain specialised medical or surgical procedures, its authors said.

Just as some rogue proteins can cause additional rogue proteins to form in the brain, such as the prions that produce mad cow disease, the new findings suggest that there may be a seed that carries the abnormal protein that drives Alzheimer’s disease. The paper was published in September in the journal “Nature”.

However, the study’s lead author took pains to emphasise that the findings do not mean that Alzheimer’s disease is contagious. Other scientists sounded even more cautious, with some expressing deep scepticism about the scope of the study and its findings.

John Collinge, a professor of neurology at University College London who was the study’s lead author, emphasised that the observational study focused on a small group of people who were unwittingly infected with Creutzfeldt-Jakob disease (CJD) when they were given contaminated, human-derived growth hormone as children.

Prior to 1985, the growth hormone was manufactured from extracts of tissue taken from the pituitary glands of cadavers, many of which were infected with prions that cause CJD, which steadily destroys brain tissue.

In examining the brains of several of those people who later died of CJD, the scientists were startled to find that many of them also had build-ups of amyloid beta, an abnormal protein that can set the process of Alzheimer’s in motion. The deposits of amyloid beta were striking, given that the people had died at relatively young ages, Collinge said. His team concluded that a plausible explanation for the build-up was that the seeds of beta amyloid had been transmitted along with the fatal prions of CJD.

His team’s work suggested that further research is needed to explore the possibility that the rogue protein that triggers Alzheimer’s disease could be transmitted through extracts of human tissue, certain kinds of transplants or perhaps improperly sterilised surgical instruments.

“I don’t think there needs to be any alarm that we’re saying any way that you can catch Alzheimer’s disease,” Collinge told reporters. “It’s simply referring to the induction of this pathology in the brain following these injections of tissue extracts.”

Others greeted the research with doubt.

David Allsop, professor of neuroscience at the University of Lancaster, expressed concern that news coverage of the study could easily mislead people into thinking Alzheimer’s is contagious, and he listed several shortcomings of the study, including the fact that there was no way of knowing whether any of the subjects would have gone on to develop Alzheimer’s.

Allsop said another possible explanation of the amyloid deposits could be that the accumulation of rogue prion proteins triggered the accumulation of beta amyloid. Other studies have shown that rogue proteins can predispose the body to accumulate additional misshapen proteins, he said.

“There is no evidence that Alzheimer’s disease can be transmitted from one person to another, or through the use of contaminated surgical instruments, and these results should be interpreted with a great deal of caution,” Allsop said in a written statement.

But others viewed the research as a significant discovery that could open up new avenues of research into Alzheimer’s and other diseases of the brain.

“I think scientifically it’s very interesting because it speaks to the movement of pathology from one place to another, which is a really interesting part of neurodegenerative diseases,” said William Rebeck, a professor of neuroscience at Georgetown University’s Medical School. “I think there’s nothing to worry about. It’s a procedure that long since stopped, and even then it affected a diminishingly small number of people.”

Alzheimer’s is the leading cause of dementia. A recent report on the global dimensions of Alzheimer’s disease says the overall shift towards older societies on the planet means that 9.9 million people will develop dementia every year, a faster pace than previously estimated. More than 5 million people in the United States have the disease, and that number is expected to nearly triple by 2050.

The hallmarks of Alzheimer’s disease are the build-up of plaques, which are formed from amyloid beta protein, and neurofibrillary tangles, which are produced by tau protein. The deposits first disrupt the brain’s memory and learning centres as they steadily destroy brain cells until death results.

The researchers made the discovery of a possible amyloid beta seed while investigating neurodegenerative diseases caused by prions. These misshapen proteins cause diseases such as scrapie in sheep and goats, bovine spongiform encephalopathy, which is more commonly known as mad cow disease, or CJD in humans, according to the Britain’s National Prion Clinic.

The majority of CJD cases occur spontaneously for no known reason. In rare cases they are caused by a faulty gene, some medical treatments, or surgical procedures such as transplants, or by eating contaminated food. Normally, prions are broken down by the body by enzymes after they have served their purpose, but misshapen prions are resistant to breakdown and can survive ordinary sterilisation procedures.

Collinge’s team conducted postmortem examinations on the brains of eight deceased people who had acquired CJD through contaminated growth hormone. The people — who died between the ages of 36 and 51 — had all been treated as children with growth hormone because they were short in stature.

Thousands of pituitary glands were collected from cadavers to produce the growth hormone, and some contained prions — misfolded proteins that seem relatively indestructible and cause the formation of others that ultimately destroy the brain.

What was startling, Collinge said, was that the team found that four of these brains also showed a “substantial build-up” of beta amyloid in brain tissues, despite the fact that the people had been relatively young when they died. Two of the others had sparser build-ups. Only one lacked signs of amyloid beta build-up. None had shown the tau tangles.

“So this was a highly unusual finding, because you wouldn’t usually expect to see amyloid deposit in this age group,” Collinge told reporters.

The paper says 1,848 people were treated with human-derived growth hormone in Britain between 1959 and 1985, when it was discovered that some of the extracts had been contaminated with CJD-causing prions. Treatments using human-derived growth hormone were terminated and replaced with synthetic hormones. But the long incubation period for CJD meant that some people developed the disease 30 or 40 years later.

A Food and Drug Administration memo in 1987 said that about 7,700 children received human-derived growth hormone between 1963 and 1985. An undetermined number of people may also have used the drug to boost athletic performance, the memo says. As of 2012, a total of 450 people have been diagnosed with CJD that was transmitted as a result of human pituitary-derived hormone treatments, surgery or invasive medical devices, the paper says.

–Washington Post