Historical medical treatment found to 'transmit' Alzheimer's

Alzheimer’s disease is caused by the amyloid-beta protein, and is usually a sporadic condition of late adult life or, more rarely, an inherited condition that occurs due to a faulty gene. Now a new study, published in the journal Nature Medicine, has provided the first known evidence of Alzheimer’s disease in living people that appears to have been acquired as a result of previous medical treatments, due to transmission of the amyloid-beta protein.

The people described in the paper had all been treated as children with a type of human growth hormone extracted from pituitary glands from deceased individuals (cadaver-derived human growth hormone, or c-hGH). This was used to treat at least 1848 people with short stature in the UK, beginning in 1959. It was withdrawn in 1985 after it was recognised that some c-hGH batches were contaminated with prions (infectious proteins) which had caused Creutzfeldt-Jakob disease (CJD), a degenerative brain disorder, in some people. c-hGH was then replaced with synthetic growth hormone that did not carry the risk of transmitting CJD.

Researchers at University College London (UCL) and University College London Hospitals NHS Foundation Trust (UCLH) had previously reported that some patients with CJD due to c-hGH treatment (called iatrogenic CJD) had prematurely developed deposits of the amyloid-beta protein in their brains. The scientists went on to show in a 2018 paper that archived samples of c-hGH were contaminated with amyloid-beta protein and, despite having been stored for decades, transmitted amyloid-beta pathology to laboratory mice when it was injected. They suggested that individuals exposed to contaminated c-hGH, who did not succumb to CJD and lived longer, might eventually develop Alzheimer’s disease.

The latest paper reports on eight people referred to UCLH’s National Prion Clinic at the National Hospital for Neurology and Neurosurgery in London, who had all been treated with c-hGH in childhood, often over several years. Five of these people had symptoms of dementia, and either had already been diagnosed with Alzheimer’s disease or would otherwise meet the diagnostic criteria for this condition; another person met criteria for mild cognitive impairment. Biomarker analysis supported the diagnosis of Alzheimer’s disease in two patients and was suggestive of Alzheimer’s in one other person; an autopsy analysis showed Alzheimer’s pathology in another patient.

The unusually young age at which these patients developed symptoms (between 38 and 55 years old) suggests they did not have the usual sporadic Alzheimer’s that is associated with old age. In the five patients in whom samples were available for genetic testing, the team ruled out inherited Alzheimer’s disease.

Here in Australia, leading Alzheimer’s researcher Professor Colin Masters and colleague Professor Steve Collins, who lead the Australian National Creutzfeldt-Jakob Disease Registry at The Florey Institute of Neuroscience and Mental Health, are calling for diagnostic blood tests for any Australians who might have undergone similar procedures to those in the UK. Masters said cadaver-derived hormones were used in Australia for short stature as well as fertility treatment; as a result, four women contracted and died from CJD in the 1980s and 2500 people who received hormone treatment are known to be at risk of CJD.

“Given the Nature Medicine article findings, we recommend screening anybody who received hormones derived from human pituitary glands for Alzheimer’s disease,” Masters said. “Fortunately, it appears that blood tests are useful in detecting early onset Alzheimer’s disease. Testing this group would be a cost-effective way of checking this at-risk population and determining the extent of risk.”

Masters, who discovered the origin of the amyloid-beta protein that causes Alzheimer’s disease, said the first evidence of potential transmissibility of Alzheimer’s emerged about 50 years ago, around the time that the prion diseases kuru and CJD were shown to be transmissible.

“Alzheimer’s disease proved not to be easily transmissible, although amyloid-beta showed some properties that, under certain conditions, it could propagate after inoculation,” he said.

“We are now faced with a serious public health issue where large numbers of people may be at risk of developing early onset Alzheimer’s because of childhood exposures through amyloid-beta-contaminated neurosurgical instruments and implants, or treatments with human cadaveric pituitary-derived hormones.

“Fortunately, new disease modifying therapies for Alzheimer’s disease are becoming available,” he said. Furthermore, as c-hGH treatment is no longer used, there is no risk of any new transmission via this route.

The researchers emphasised that there have been no reported cases of Alzheimer’s acquired from any other medical or surgical procedures, and there is no suggestion that amyloid-beta can be passed on in day-to-day life or during routine medical or social care. However, they said their findings highlight the importance of reviewing measures to ensure there is no risk of accidental transmission of amyloid-beta via other medical or surgical procedures which have been implicated in accidental transmission of CJD.

“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 study co-author Professor Jonathan Schott, from the UCL Queen Square Institute of Neurology.

“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.”

Image credit: iStock.com/Eoneren