Sections of mouse brains from the 2018 study. Top line shows control subjects inoculated with synthetic growth hormone, lower two lines show subjects inoculated with c-hGH. E and h show CAA while f and i show amyloid beta plaque deposition. Credit: Purro et al, 2018/UCL
Five middle-aged people have been diagnosed with Alzheimer’s disease as a result a now-discontinued medical treatment the patients received in childhood, according to a new study. This is the first evidence of Alzheimer’s disease in living people that appears to have been medically acquired.
Alzheimer’s disease is typically caused by a buildup of amyloid-beta protein as an individual ages. However, these patients appear to have acquired the disease in middle age due to transmission of the amyloid-beta protein as part of medical treatment decades prior.
The patients described in the new Nature Medicine paper, now between 38 and 55 years old, had all been treated as children with a type of human growth hormone extracted from pituitary glands from deceased individuals—known as cadaver-derived human growth hormone, or c-hGH.
c-hGH was used to treat at least 1,848 people in the UK between 1959 and 1985 for various causes of short stature. It was withdrawn in 1985 after scientists recognized that some c-hGH batches were contaminated with prions (infectious proteins) after some patients contracted Creutzfeldt-Jakob disease (CJD).
This latest paper focuses on eight people 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 them had symptoms of dementia, and either had already been diagnosed with Alzheimer’s disease or would otherwise meet the diagnostic criteria. A sixth person met the criteria for mild cognitive impairment.
All patients were between 38 and 55 years old when they started displaying neurological symptoms. The unusually young age at which the symptoms developed suggests the patients did not have the typical Alzheimer’s, which is associated with old age. Additionally, for five patients in which samples were available for genetic testing, researchers were able to rule out inherited Alzheimer’s disease.
As c-hGH treatment is no longer used, there is no risk of any new transmission via this route. There have been no reported cases of Alzheimer’s acquired from any other medical or surgical procedures.
“There is no suggestion whatsoever that Alzheimer’s disease can be transmitted between individuals during activities of daily life or routine medical care. The patients we have described were given a specific and long-discontinued medical treatment which involved injecting patients with material now known to have been contaminated with disease-related proteins,” said lead author John Collinge, director of the University College London Institute of Prion Diseases and a consultant neurologist at University College London Hospital.
However, the researchers caution that 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.
In 2018, the same team of researchers showed that archived samples of c-hGH were contaminated with amyloid-beta protein and—despite having been stored for decades—still transmitted amyloid-beta pathology to laboratory mice when injected. The scientists proposed then that individuals exposed to contaminated c-hGH who did not succumb to CJD in the immediate aftermath might eventually develop Alzheimer’s disease.
These newest results suggest the researchers’ 2018 hypothesis was correct.
Overall, the results could have implications for understanding and treating Alzheimer’s disease in the future, as well as other neurological conditions share similar disease processes to CJD.