Alzheimer’s can be spread from human to human through rare medical accidents, research suggests, although experts stress there is no evidence the disease can be passed between people through everyday activities or routine care, and it is not transmissible, like a viral or bacterial infection.
The scientists say a handful of people who received human growth hormone from the pituitary glands of deceased donors have gone on to develop early onset Alzheimer’s – probably because the hormones used were contaminated with proteins that seeded the disease in their brains.
“We’re not suggesting for a moment you can catch Alzheimer’s disease. This is not transmissible in the sense of a viral or bacterial infection,” Professor John Collinge, co-author of the study and director of the MRC Prion Unit at University College London, told The Guardian.
“It’s only when people have been accidentally inoculated, essentially, with human tissue or extracts of human tissue containing these seeds, which is thankfully a rare and unusual circumstance.”
The team says the new work adds weight to the idea that Alzheimer’s has similarities with prion diseases, including in the mechanism by which the proteins involved spread across the brain.
Prion diseases, which include Creutzfeldt-Jakob disease (CJD), the rare and fatal blood disorder called kuru, and bovine spongiform encephalopathy (BSE), are caused by infectious, misfolding proteins which propagate in the brain. These diseases typically occur spontaneously, however, more rarely, they can arise from a genetic mutation, or be transmitted via infected brain or nervous tissue.
Writing in the journal Nature Medicine, Collinge and colleagues report how between 1959 and 1985, at least 1 848 patients in the UK received human growth hormone extracted from the pituitary glands of cadavers.
But the practice was banned in 1985 after it emerged some patients subsequently died of CJD as a result of hormone samples contaminated with CJD-causing proteins.
Of the 80 such cases in the UK, some were also found to have a protein called amyloid-beta in their brains when they died – a hallmark of Alzheimer’s disease.
While it was unclear if they would have gone on to develop symptoms of Alzheimer’s, other research showed amyloid-beta was present in some of the hormone batches, and that these triggered Alzheimer’s-like disease if administered to mice.
Researchers have reported findings from all eight people referred to the National Prion Clinic between 2017 and 2022.
All received human growth hormone from cadavers, but did not have CJD. Five had dementia symptoms meeting clinical criteria for Alzheimer’s disease, with onset as young as 38-years-old.
Three of these patients had brain scans consistent with the diagnosis, while two had biomarkers that met criteria for Alzheimer’s.
Of the other three patients, one had mild cognitive impairment, one had self-reported cognitive difficulties, and one had no such symptoms, with the former showing post-mortem results consistent with Alzheimer’s and the latter meeting biomarker criteria for the disease.
Five patients had DNA data, but only one showed a genetic risk factor for late onset Alzheimer’s, and none had genetic variants known to cause early onset Alzheimer’s.
The researchers add the patients showed some symptoms that differed from those typical for Alzheimer’s disease, which either spontaneously arises or is linked to genetic risk, positing this could either be down to their disease having a different origin, or arising from different “strains” of amyloid-beta.
The results, they say, offer evidence that Alzheimer’s can arise as a result of treatment with the contaminated pituitary hormone.
While the cases involved repeated exposure to contaminated human growth hormone over a period of years, Collinge and colleagues say the findings raise the importance of measures such as ensuring effective decontamination of surgical instruments.
However, Andrew Doig, professor of biochemistry at the University of Manchester, said experts were already very careful about transmitting brain tissue between people.
Doig also cautioned that only eight patients were involved in the study, some of whom lacked genetic data, while as yet there was no direct evidence for different strains of amyloid-beta.
“While the new type of Alzheimer’s reported here is of great scientific interest, as it reveals a new way to spread the disease, there is no reason to fear it, as the way in which the disease was caused was stopped more than 40 years ago,” he said.
“Disease transmission from human brain to brain in this way should never happen again.”
Study details
Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone
Gargi Banerjee, Simon Farmer, John Collinge, et al.
Published in Nature Medicine on
Abstract
Alzheimer’s disease (AD) is characterised pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms. Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance.
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