For the first time, cases of Alzheimer's disease acquired through infection have been described
Scientists have identified five cases of Alzheimer's disease resulting from amyloid protein contamination from treatments decades earlier. These unique precedents will help redefine the link between prion diseases and Alzheimer's disease.
One of the main causes of Alzheimer's disease is the accumulation of a pathogenic form of beta-amyloid protein in the brain. The disease usually occurs sporadically due to the accumulation of mutations towards the end of adulthood or - less commonly - due to an inherited defective gene. A new paper published in Nature Medicine presents cases of Alzheimer's disease acquired after medical intervention long before the first manifestations of the disease and caused by the transmission of a pathogenic form of beta-amyloid protein.
All of the patients described in the article, as children, received human growth hormone isolated from the pituitary glands of deceased individuals. This method was used to treat various causes of short stature in at least 1,848 people in the UK from 1959 to 1985. It was later abandoned when it was discovered that some batches of such hormones were contaminated with defective prions (abnormal proteins twisted into a pathogenic form) that caused the deadly prion disease Creutzfeldt-Jakob disease. Subsequently, growth hormone from dead humans was replaced with a synthetic analog that carried no risk of transmitting pathogenic forms of prions.
In earlier papers, the scientists reported that some patients with Creutzfeldt-Jakob disease due to cadaveric growth hormone treatment prematurely developed beta-amyloid protein deposits in the brain. Also in another paper, the authors showed that archived growth hormone samples from dead people contaminated with beta-amyloid protein, even decades later, transmitted the beta-amyloid pathology to laboratory mice when injected. So the scientists hypothesized that people exposed to the contaminated hormone who did not get Creutzfeldt-Jakob disease and lived longer might eventually develop Alzheimer's disease.
The authors of the new paper reported on eight people treated with cadaveric growth hormone during childhood, often for several years. Five of them had symptoms of dementia with already diagnosed Alzheimer's disease or met diagnostic criteria for the condition. Another patient fit the criteria for moderate cognitive impairment. They were all between 38 and 55 years old when the neurologic symptoms appeared. Biomarker analysis confirmed the diagnosis of Alzheimer's disease in two people, and predicted the onset of the disease in another. In another case, the presence of Alzheimer's disease was confirmed by a postmortem autopsy.
The unusually young age at which these patients began to develop symptoms, together with the fact that they had been treated with growth hormone from dead people as children, suggested that they did not have the usual sporadic Alzheimer's disease that often occurs with age in modern people. In addition, the research team ruled out hereditary Alzheimer's disease in five patients whose samples were available for genetic testing. All of this reinforced the conclusion: the cause of Alzheimer's disease in the cases described was the transmission of a pathogenic form of beta-amyloid during treatment in childhood.
The circumstances under which these individuals tragically developed Alzheimer's disease are highly unusual. Since growth hormone treatment from dead people is no longer practiced, there is no risk of any new transmission in this way. There are no reported cases of Alzheimer's disease acquired through any other medical or surgical procedures to date. Nor is there any suggestion that beta-amyloid can be transmitted in everyday life or during routine medical or social care.
The results show that Alzheimer's disease and some similar neurological diseases share pathologic processes with Creutzfeldt-Jakob disease. This may prompt the development of new treatment strategies for dementias associated with the pathologic form of beta-amyloid protein.