It has long been suspected that Alzheimer's could be transmissible in rare cases - for example, when misfolded amyloid proteins get directly into the brain or blood of recipients. Now a study provides new evidence for this form of transmission. Researchers in Great Britain have identified five cases of unusually early onset Alzheimer's dementia in patients, all of whom had received a special, now banned medical therapy as children: all of them had been given human growth hormones obtained from the dead, which were probably linked to pathologically misfolded amyloid beta proteins were contaminated. While the potential transferability of such preparations had previously been demonstrated in mice, the five patients now confirm that this can actually trigger Alzheimer's dementia in humans.
The suspicion is not new: Scientists have long suspected that Alzheimer's disease could be similar in certain aspects to a prion disease such as BSE or Creutzfeld-Jakob disease (CJD). In these cases, misfolded proteins are the triggers that can transfer their misfolding to other proteins that are still correctly formed. As a result, these proteins called prions act like an infectious pathogen and can also transmit the respective disease to other individuals. “The potential importance of such prion mechanisms has increased significantly when it was recognized that more common neurodegenerative diseases such as Alzheimer's and Parkinson's are also linked to the accumulation and proliferation of misfolded proteins,” explain Gargi Banerjee from University College London and his colleagues. “Their spread is also often described as prion-like.”
In recent years, scientists have actually found several indications that the misfolded amyloid proteins from Alzheimer's sufferers can transfer their misfolding to healthy proteins in a similar way to prions. Mice developed Alzheimer's disease after receiving injections directly into the brain containing amyloid beta plaques. Another study found evidence that some people developed Alzheimer's after being implanted with meninges contaminated with misfolded proteins during brain surgery. However, in all of these cases, transmission only occurred if the malformed amyloid proteins had reached the recipient's brain directly - which is extremely rare in everyday medical practice.
Alzheimer's caused by growth hormones, which are now banned
As early as 2015, however, the suspicion arose that prion-like transmission in Alzheimer's disease could also occur via the blood. Evidence for this came from observations of patients who, as children, had received human growth hormones obtained from the tissue of dead people because of their short stature. These preparations were used until 1985, but were then banned because the risk was too high: some batches were contaminated with prions of Creutzfeld-Jakob disease, causing 80 cases of this incurable, fatal neurodegenerative disease in Great Britain alone. When researchers examined the brains of some of these patients who died of CJD between the ages of 36 and 51 in more detail, they discovered something striking: despite their relatively young age, the amyloid plaques typical of Alzheimer's were already visible in the patients' brains. Even then, this raised suspicions that these patients could have been infected not only with CJD, but also with Alzheimer's via the growth hormone.
However, it has so far remained unclear whether such a transfer of misfolded amyloid proteins and the subsequent formation of plaques can actually trigger Alzheimer's dementia. The study by Banerjee and his team now provides evidence of this. They examined eight patients who had received potentially contaminated growth hormones as children but had not been infected with Creutzfeld-Jakob disease. However, five of these patients developed symptoms of Alzheimer's dementia at an unusually young age: Although they were only between 38 and 55 years old and had no genetic predisposition to Alzheimer's, they experienced the cognitive deficits and progressive deficits typical of this dementia, such as Researchers report. Another patient showed early milder symptoms of dementia but was not clearly diagnosed with Alzheimer's disease.
No risk of transmission in everyday life
According to Banerjee and his colleagues, there is evidence to suggest that these patients did not develop Alzheimer's by chance, but rather as a result of contaminated growth hormones: "Their relatively young age makes sporadic Alzheimer's disease unlikely and we have ruled out genetic causes," explain it. “Therefore, we assume that their symptoms and biomarker findings are a result of amyloid beta transmission through the contaminated human growth hormones that these people received in childhood.” This is further evidence that Alzheimer's disease is transmitted through the misfolded amyloid beta proteins. “Our results therefore suggest that Alzheimer’s and other neurological diseases are based on similar processes as Creutzfeld-Jakob disease,” says senior author John Collinge from University College London. “This could also be important for understanding and treating Alzheimer’s disease.”
However, it is important to know that the form of transmission examined here can no longer occur today: growth hormones are now produced synthetically, and their extraction from the pituitary gland of dead people has been banned worldwide since 1985. There is also no risk of transmission during normal medical treatments or dealing with Alzheimer's patients: "There is no evidence that Alzheimer's can be transmitted during activities of daily life or during normal medical care," emphasizes Collinge. “The patients we have described here received a specific therapy that had not been used for a long time, in which - as we now know - material contaminated with disease-causing proteins was injected.” Knowledge of these cases is therefore particularly important for them Alzheimer's research and also for hygiene guidelines, for example for brain operations.
Source: Gargi Banerjee (University College London) et al., Nature Medicine, doi: 10.1038/s41591-023-02729-2