A medical treatment given to children in the UK may have led to some developing Alzheimer’s disease decades later, new research out Monday suggests. The study presents evidence that at least five people contracted the neurodegenerative disorder from having received human growth hormones contaminated with rogue amyloid beta protein. The authors point out that Alzheimer’s cannot be caught person-to-person through conventional means, however, and this specific infection risk no longer exists today.
Starting in the 1950s, scientists learned how to extract human growth hormone (HGH) from the pituitary glands of cadavers. Unfortunately, the method only provided minute amounts of hormone at a time, which limited the supply of HGH available for medical and research purposes. As a result, its distribution was meticulously handled, and it was typically only given to treat the most severe growth-related conditions in children.
This remained the status quo for the next 30 years, with more than 20,000 children worldwide having received this form of cadaver-derived HGH. But in the mid-1980s, health officials in the U.S. and elsewhere began to get unusual reports of people coming down with Creutzfeldt-Jakob disease (CJD), a rare but universally fatal neurodegenerative disease. These cases were happening in much younger people than typically seen with CJD, and it was soon discovered those affected shared a history of past HGH treatment. Within months of this discovery, the U.S. and other countries shut down their cadaver HGH programs.
These cases, as it turned out, were caused by HGH seeded with a person’s misfolded prions—mutinous proteins that eat away at the brain by gradually transforming normal prions into their misfolded form. It can take years to decades before the symptoms of a prion disease appear, explaining why it took so long for the connection to be discovered. As of today, there have been around 220 cases of Creutzfeldt-Jakob disease linked to cadaver-derived HGH, with some showing up to 40 years later.
Researchers at the University of College London have continued to keep track of potential cases of illness tied to HGH. And over time, they’ve come across patients who seem to have avoided CJD but have developed other neurological conditions, including Alzheimer’s disease. In a paper published in Nature Medicine Monday, they argue that these cases represent a rare but real form of transmissible Alzheimer’s.
The paper details eight patients who visited the UCL’s National Prion Clinic. Five of them appear to have developed early onset Alzheimer’s, with a sixth having mild cognitive impairment. But none of the patients seemed to have known genetic mutations that cause Alzheimer’s to happen at a younger age or other shared factors besides a past history of HGH treatment.
Alzheimer’s is caused by the build-up of two misfolded proteins in the brain, amyloid beta and tau, with amyloid beta seen as the driving force of the two. The team’s past research has found amyloid beta inside the brains of people who died from HGH-caused Creutzfeldt-Jakob disease, as well as inside samples of preserved HGH. And in the lab, they’ve been able to successfully cause mice to develop Alzheimer’s-like illness after exposing them to these contaminated samples.
Put all the pieces together, the study authors say, and it’s enough to show that “Alzheimer’s disease should now be recognized as a potentially transmissible disorder.”
The team’s work is the latest to suggest that Alzheimer’s and other neurodegenerative conditions have a lot in common with prion diseases like CJD (some scientists have even argued that they effectively are prion diseases). Prion diseases are usually inherited or occur spontaneously, for instance, but have rarely been transmitted through contaminated beef or the ritualistic cannibalism of human brains, in addition to HGH treatments. At the same time, people shouldn’t be worried about catching Alzheimer’s or prion diseases like they would a typical infectious germ, like a virus. And scientists eventually learned how to synthesise HGH in the lab, and this version was given regulatory approval soon after the cadaver programs were shut down.
“It is important to stress that the circumstances through which we believe these individuals tragically developed Alzheimer’s are highly unusual, and to reinforce that there is no risk that the disease can be spread between individuals or in routine medical care,” said the study author Jonathan Schott, a UCL neurologist and chief medical officer at Alzheimer’s Research UK, in a statement from the university. “These findings do, however, provide potentially valuable insights into disease mechanisms, and pave the way for further research which we hope will further our understanding of the causes of more typical, late onset Alzheimer’s disease.”