A recent study has uncovered a potential correlation between previous medical treatment involving contaminated human growth hormone and the early onset of Alzheimer’s disease in five individuals. This serves as a stark reminder of the significance of preventing inadvertent amyloid-beta transmission in medical procedures.A team of researchers from UCL and UCLH has documented five cases of Alzheimer’s disease potentially linked to medical treatments administered several decades ago. Alzheimer’s disease is typically associated with the amyloid-beta protein and is commonly a sporadic condition occurring in late adult life, or less frequently, an inherited condition resulting from a faulty gene. The new research, published in Nature Medicine, presents the first evidence of Alzheimer’s disease in living individuals that seems to have been acquired through medical means and due to the transmission of the amyloid-beta protein.These individuals had all received treatment 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 treatment was administered to at least 1,848 people in the UK between 1959 and 1985 to address various causes of short stature. It was discontinued in 1985 after it was discovered that some c-hGH batches were contaminated with prions (infectious proteins) that had caused Creutzfeldt-Jakob disease (CJD) in some individuals. c-hGH was subsequently replaced with synthetic growth hormone, eliminating the risk of transmitting CJD.Link Between c-hGH and Alzheimer’s DiseasePrevious research by these scientists indicated that some patients with CJD due to c-hGH treatment (referred to as iatrogenic CJD) had prematurely developed deposits of the amyloid-beta protein in their brains.* The researchers further demonstrated in a 2018 study that archived samples of c-hGH were contaminated with amyloid-beta protein and, despite being stored for decades, conveyed amyloid-beta pathology to laboratory mice when injected.** They proposed that individuals exposed to contaminated c-hGH, who did not succumb to CJD and had longer life expectancies, might eventually develop Alzheimer’s disease.In this latest study, eight individuals who had all been treated with c-hGH during childhood, often over several years, were examined at UCLH’s National Prion Clinic at the National Hospital for Neurology and Neurosurgery in London. Five of these individuals exhibited symptoms of dementia and had either already been diagnosed with Alzheimer’s disease or would otherwise meet the diagnostic criteria for the condition; one other individual met the criteria for mild cognitive impairment. These individuals started experiencing neurological symptoms between the ages of 38 and 55. Biomarker analyses confirmed the diagnoses of Alzheimer’s disease in two patients and suggested the presence of Alzheimer’s in another individual; autopsy analysis revealed Alzheimer’s pathology in one patient.The early onset of symptoms in these patients suggests that they did not have the typical sporadic Alzheimer’s associated with old age. In the five patients who were tested for genetic predispositions, inherited Alzheimer’s disease was ruled out.Since c-hGH treatment is no longer in use, there is no risk of further transmission through this avenue. There have been no reported instances of Alzheimer’s being acquired from any other medical or surgical procedures. There is no indication that amyloid-beta can be transmitted in everyday life or during routine medical or social care.Implications and RecommendationsHowever, the researchers caution that their findings emphasize the need to reassess precautions to ensure there is no risk of inadvertent transmission of amyloid-beta through other medical or surgical procedures that have been implicated in the accidental transmission of CJD. The lead author of the study, Professor John Collinge, Director of the UCL Institute of Prion Diseases and a consulting neurologist at UCLH, stated: “There is absolutely no indication that Alzheimer’s disease can be transmitted between individuals during daily activities or routine medical care. The patients we have described were subjected to a particular and long-discontinued medical treatment that involved administering material now known to have been contaminated with disease-related proteins.“However, the recognition of amyloid-beta pathology transmission in these rare situations should prompt us to reevaluate measures to prevent inadvertent transmission through other medical or surgical procedures in order to avert such cases in the future.“Significantly, our findings also suggest that Alzheimer’s and certain other neurological conditions share similar disease processes with CJD, which may have important implications for understanding and treating Alzheimer’s disease in the future.”Co-author Professor Jonathan Schott (UCL Queen Square Institute of Neurology, consulting neurologist at UCLH, and Chief Medical Officer at Alzheimer’s Research UK) said: “It is important to emphasize that the circumstances under which we believe these individuals tragically developed Alzheimer’s are highly unusual, and to reiterate that there is no risk of the disease spreading between individuals or in routine medical care. However, these findings do present potentially valuable insights into disease mechanisms and pave the way for further research that we hope will advance our understanding of the causes of more typical, late-onset Alzheimer’s disease.”The lead author Dr Gargi Banerjee (UCL Institute of Prion Diseases) stated: “We have discovered that it is feasible for amyloid-beta pathology to be transmitted and contribute to the development of Alzheimer’s disease. This transmission occurred as a result of treatment with an outdated form of growth hormone and entailed repeated administration of contaminated material over several years. There is no indication that Alzheimer’s disease can be acquired through close contact or during the provision of routine care.”Reference: “Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone” by Gargi Banerjee, Simon F. Farmer, Harpreet Hyare, Zane Jaunmuktane, Simon Mead, Natalie S. Ryan, Jonathan M. Schott, David J. Werring, Peter Rudge and John Collinge, 29 January 2024, Nature Medicine.
DOI: 10.1038/s41591-023-02729-2The study received support from the Medical Research Council, the National Institute for Health and Care Research (NIHR), the NIHR UCLH Biomedical Research Centre, Alzheimer’s Research UK, and the Stroke Association.
