(CTN News) – New research shows five people in the UK were diagnosed with Alzheimer’s disease (AD) from decades-old medical treatment.
It’s the first known case of medically acquired AD in living people, but outside experts say the findings need to be interpreted carefully.
A pituitary gland from cadavers (c-hGH) was used to treat the individuals as children. 30,000 people, mostly children, got treatment with c-hGH between 1958 and 1985 for genetic disorders and growth hormone deficiency.
After three Americans who received the treatment died of Creutzfeldt-Jakob disease (CJD) after batches of c-hGH contaminated with disease-causing prions, the therapy was stopped in 1985.
A couple of years ago, the researchers discovered that c-hGH batches also contained amyloid-beta protein, which could be transmitted decades later. Researchers and clinicians at a prion clinic led by one of the lead researchers referred or reviewed these five cases.
Researchers say there are no reports of amyloid-beta being transmitted through other medical or surgical procedures, and there’s no evidence that amyloid-beta can spread in daily activities.
“However, the recognition of amyloid-beta transmission in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, to prevent such cases from happening again,” a press release said. John Collinge, MD, director of UCL’s Institute of Prion Diseases and head of the National Prion Clinic, is the lead author.
“We also found that Alzheimer’s and some other neurological conditions share similar disease processes to CJD, which could be important for understanding and treating Alzheimer’s disease,” Collinge said.
Nature Medicine published the findings online on January 29.
A previous 2015 study found that archived c-hGH samples were also contaminated with amyloid-beta protein. A study in 2018 showed that c-hGH samples stored for decades could still transmit amyloid-beta.
They said the findings suggested that people who didn’t die from CJD might develop AD after being exposed to contaminated c-hGH.
Between 2017 and 2022, patients at the National Prion Clinic in the UK developed neurologic symptoms consistent with AD.
Between 2017 and 2022, expert doctors referred or reviewed the cases. The clinic coordinates the National Prion Monitoring Cohort, a longitudinal study of people with confirmed prion diseases.
Three patients were diagnosed with AD before referral; two met the criteria for AD diagnosis, and three did not meet the criteria. Three of the patients, two of whom had AD, died.
In the study, c-hGH was prepared using Wilhelmi or Hartree-modified Wilhelmi preparation (HWP).
Another two cases showed progressive brain volume loss on brain imaging, elevated total tau and phosphorylated tau levels in cerebrospinal fluid, and amyloid-beta deposits on autopsy.
Different patients showed up for the study. Some were not symptomatic, while others didn’t meet current Alzheimer’s disease diagnostic criteria.
Treatment duration and frequency differed among them, as did their ages at the start and end of treatment. Other factors likely contributed to the different phenotypes recorded in individuals, researchers said.
Researchers examined and ruled out other factors that might explain the individuals’ cognitive symptoms, including childhood intellectual disability linked with dementia risk and growth hormone deficiency, which led to c-hGH treatment and cranial radiotherapy for four of the individuals.
All five cases with samples available for testing were also ruled out for inherited diseases.
The authors write that all the patients in this study were treated with HWP c-hGH. We conclude that the findings observed are most plausible if [amyloid-beta] transmission is the most plausible explanation given the strong experimental evidence for [amyloid-beta] transmission from HWP c-hGH batches.”
AD is thought to have three etiologies, like other prion diseases: sporadic, inherited, and rare acquired forms.
“Alzheimer’s disease should now be recognized as a potentially transmissible disease because of the clinical syndrome that these people developed,” the authors wrote.
“As with human prion diseases, we found that iatrogenic Alzheimer’s disease differs phenotypically from sporadic and inherited forms. There are protective factors that aren’t known, but some people remain asymptomatic despite exposure to [amyloid-beta] seeds,” they wrote.
A companion editorial was written by Mathias Jucker, PhD, of the Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, and Lary C. Emory University’s Department of Neurology’s Dr Walker said they should be taken with a measure of scepticism..”
“These are complex and diverse cases; all of the people involved had been treated for a variety of illnesses earlier in life, and it’s hard to exclude that these circumstances contributed to their complicated disease phenotypes,” they wrote.
They say, “There are good reasons to take the findings seriously.”
“It reinforces the potential of amyloid-[beta] seeds for early prevention, as well as the need for informed caution when handling surgical instruments, tissues, and therapeutic biologics, particularly those from people.”
Study Reveals Cases of Medically Acquired Alzheimer’s Disease in the UK
According to Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, the idea that amyloid-beta is transmissible between people has been proven before.
By injecting amyloid-beta into an animal’s brain, we’ve known for a long time that it’s possible to make amyloid buildup like Alzheimer’s.
Moreover, we transfer human Alzheimer’s genes into animals to cause brain changes that look like Alzheimer’s. “Thus, the idea of amyloid being transferable between people isn’t as new as the new paper suggests.”
Weber said that the study highlights the importance of safety measures to prevent accidental transmission of amyloid-beta.
Scientists and clinicians need to understand the possible risks and ensure all transmission methods are eliminated, such as sterilizing surgical instruments completely and conscientiously, he says.
Ultimately, we shouldn’t put amyloid-beta in people’s brains, either accidentally or on purpose, and we must ensure we don’t do it.
Medical Research Council, National Institute for Health and Care Research (NIHR), University College of London Hospital Biomedical Research Centre, Alzheimer’s Research UK, and Stroke Association funded the study. Jucker and Walker report no conflicts of interest. Collinge’s stockholder and director is D-Gen, Ltd., an academic spin-off company that diagnoses, decontaminates, and cures prion diseases.