Alzheimer’s disease may, rarely, be transmitted by medical treatment
Childhood treatment with contaminated human growth hormone may cause the disease years later
RESEARCHERS DIVIDE Alzheimer’s disease, the most common form of dementia, into two types. “Sporadic” cases usually occur in people over 65. Rarer “familial” ones are associated with a handful of mutations that run in families. Symptoms can begin in a patient’s 30s.
But evidence is mounting that a third, much rarer type exists as well. A paper published on January 29th in Nature Medicine describes five people with early-onset Alzheimer’s who may have contracted it from treatment with human growth hormone (HGH) given when they were children. If that is indeed what has happened, it would establish a third “iatrogenic” form of the disease—one that is transmitted by medical procedures.
The paper, by John Collinge, a neurologist at University College, London (UCL), and his colleagues, builds on previous research from the same group. But the story begins with a different malady—Creutzfeldt-Jakob disease (CJD), a fatal neurodegenerative condition best known for the variant (vCJD), dubbed “mad cow disease”, that jumped from cattle to humans in the 1990s.
In the 1980s Stanley Prusiner, a biochemist, showed that CJD, and some other, related diseases, are caused not by a bacterium or a virus, but by a defective form of one of the body’s own proteins. The defect lies in the protein’s shape rather than its chemical makeup. Before a newly created protein can do its job, it must fold itself up in exactly the right way. Sometimes that process goes wrong. Some of those misfolded proteins, dubbed “prions” by Dr Prusiner, can cause other copies of themselves to misfold in turn. Too many misfolded proteins can gum up the workings of cells and kill them.
Like Alzheimer’s, CJD is mostly either sporadic or inherited. Only around 1% of cases are transmitted. The vCJD outbreak of the 1990s was caused by eating contaminated beef. But other routes are possible, too. Between 1959 and 1985 around 30,000 people around the world, mostly children, were given injections of HGH to boost their height. The hormone was extracted from the brains of cadavers. Some, it later emerged, were contaminated with CJD-causing prions. To date, over 200 cases of CJD have been attributed to those treatments.
In 2015, while examining the brains of eight people who died in this manner, Dr Collinge found that four of the brains also contained deposits of amyloid-beta, another type of protein—but one that is associated with Alzheimer’s, not CJD. As with the prion that causes CJD, misshapen bits of amyloid-beta can cause other copies of the protein to form tangled clumps in the brain. Such clumps are a hallmark of Alzheimer’s.
Dr Collinge’s team surmised that the people in question had been doubly unlucky: their hormone injections had been contaminated not only with CJD-causing prions but with amyloid-beta clumps as well. In 2018 Dr Collinge went on to show that untouched samples of HGH that had been in storage since the 1980s contained amyloid-beta—and that injecting the stuff into mice caused their brains to develop Alzheimer ’s-like protein clumps.
Then, in 2019, a team led by Dr Gargi Banerjee, a neurologist who also works at UCL, found that three people who had received grafts of cadaveric dura mater, a thick membrane that covers the brain, were suffering from cerebral amyloid angiopathy (CAA), a condition closely related to Alzheimer’s, and one in which amyloid-beta is also implicated. Dr Banerjee argued that this too was a case of the inadvertent medical transmission of misfolded proteins.
All that adds up to a highly suggestive pile of evidence. But until now, no one had found any patients who had received contaminated HGH and gone on to develop Alzheimer’s. Dr Collinge’s latest paper—co-authored with Dr Banerjee—does just that. It reports the cases of eight people who had been referred to the National Prion Clinic at UCL, and who had received childhood HGH treatments. Biomarkers, blood tests and even autopsies (carried out on two patients who died during the course of the study) concluded that seven had at least some signs consistent with Alzheimer’s. Five had symptoms that met diagnostic criteria, and which had begun between the ages of 38 and 55.
The patients were all relatively young, making sporadic Alzheimer’s unlikely. Five had been genetically tested as part of their treatment; none carried mutations known to cause the familial form of the disease. All that strongly suggests that their childhood medication is to blame, says Dr Collinge.
“We’re not suggesting for a moment that you can catch Alzheimer’s disease [from other people],” he says. He does, though, think that medical procedures known to have transmitted CJD in the past ought to be looked at carefully. These days HGH is made synthetically, rather than being harvested from the dead. The World Health Organisation advises against human dura mater grafts. However, there have been rare cases of CJD associated with other medical treatments carried out in childhood.
If Dr Collinge is proven right, one question is what can be done to stop such transmissions in future. Prions are hardy things, and can survive routine sterilisation in an autoclave. Dr Collinge thinks the same is likely true of amyloid-beta. He and his colleagues are planning to test an enzyme-detergent mixture which they developed to destroy CJD prions to see if it works for amyloid-beta as well.
Another is what it might mean for treating Alzheimer’s, even in people in whom the disease develops spontaneously. The exact role that amyloid-beta plays in Alzheimer’s is not fully understood. But Dr Collinge believes his study suggests that “what’s going on in Alzheimer’s is very similar in many respects to what happens in human prion diseases like CJD.” That might open up new treatment possibilities for a disease that remains, for now, incurable.
© 2023, The Economist Newspaper Limited. All rights reserved. From The Economist, published under licence. The original content can be found on www.economist.com
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