Childhood hormone treatments may have spread Alzheimer’s proteins

Growth hormones given to children decades ago appear to have spread proteins linked to Alzheimer’s disease. The finding adds to evidence that Alzheimer’s proteins can be transmitted between people.

Between 1958 and 1985, approximately 30,000 children around the world received injections of human growth hormone extracted from dead bodies to treat genetic disorders and growth deficiencies.

Three years ago, while examining the brains of eight people who had received such injections and later died of the rare brain disorder Creutzfeld-Jakob disease (CJD), John Collinge at University College London and his colleagues noticed they all had beta-amyloid proteins in their brains.

Beta-amyloid is known to accumulate and form sticky plaques in the brains of people with Alzheimer’s disease. These eight people didn’t have this condition, as they all died from CJD at a young age, but Collinge says that had they lived, it’s possible that they would have gone on to develop it.

“That led us to hypothesise that the reason they got this [amyloid] is because those growth hormone batches that were prepared many years ago with human tissue were contaminated with this protein,” says Collinge. Before synthetic alternatives were available, human growth hormone was extracted from the pituitary glands of cadavers.

“Another suggestion was maybe it’s the growth hormone itself that stimulates the amyloid beta pathology, and not any contaminant,” he says. To investigate, Collinge and his team used samples of the human growth hormone that were given to these eight people, which had been archived by a health body in the UK.

Seeding disease

They found that all of the eight people had received growth hormone extracted from cadavers using one particular method. When Collinge and his team compared growth hormone prepared in this way with three other extraction methods, they found beta-amyloid proteins and tau proteins – which are also implicated in Alzheimer’s – only in samples made using this method.

To see if this exposure to Alzheimer’s proteins could have been enough to seed later disease, the team injected archived human growth hormone into the brains of mice that had been genetically engineered to be able to develop some human-like signs of Alzheimer’s disease.

These mice went on to accumulate beta-amyloid and tau proteins in their brains, as did mice that were injected with brain tissue from Alzheimer’s patients. Mice injected with synthetic growth hormone, however, did not show any signs of these proteins. Together, these results suggest some cadaveric formulations of growth hormone can indeed seed the accumulation of Alzheimer’s-related proteins.

“I was rather amazed that we could seed this so easily with this material that sat around as a dried powder for 30 or 40 years. It shows the persistence of these seeds to degradation,” says Collinge.

Long-lived proteins

The persistence of beta-amyloid may explain why its build-up in the brain is so difficult to fight, says David Holtzman at Washington University in St. Louis, Missouri. “They are stable once they form, often for the lifetime of the individual. Once these things form, they continue to grow and grow, and the body can’t get rid of it easily,” he says.

While Alzheimer’s proteins seem to be transmissible, that doesn’t mean they are contagious. “You have to come in contact with brain matter,” says Sebastian Brandner, who worked on the study. “Perhaps other transmissions through other organs may be possible. There’s no evidence of that, but there’s a huge amount of research that can be done,” he says.

In a previous study, Brandner found that eight people who developed cerebral amyloid angiopathy – a build-up of beta-amyloid proteins in the brain that can lead to bleeding – at an abnormally young age, had all undergone childhood brain surgery. He found that the surgical instruments could have transmitted the proteins.

Collinge says contamination of surgical instruments is a small risk, but one we should remove through research and better sterilisation techniques.