麻豆传媒

Human growth hormone samples extracted from cadavers decades ago were able to "seed" amyloid beta pathology in mice, researchers reported.

While these findings do not demonstrate that Alzheimer's disease can be transmitted, they provide experimental evidence for the hypothesis that amyloid beta pathology can be transmitted by iatrogenic means, said John Collinge, MD, of University College London, and colleagues, in .

"This represents a new way of thinking about Alzheimer's disease," Collinge said in a press briefing. "There may be certain circumstances -- hopefully, they're rare medical circumstances -- in which transmission of the pathology can occur."

In 2015, Collinge's group reported evidence of early amyloid beta pathology in the brains of seven people who had died of iatrogenic Creutzfeldt-Jakob disease (CJD). These patients had been treated with human growth hormone from cadaveric pituitary glands, a practice that was stopped in 1985 when some recipients were found to have developed CJD. What was unknown at the time was whether these patients developed amyloid beta pathology from the cadaveric samples or whether the samples contained amyloid beta.

Since then, Collinge and colleagues obtained vials of the growth hormone the patients were exposed to and found a number of them tested positive for both amyloid beta and tau protein. They injected samples into mice models of Alzheimer's disease and found that the animals developed accelerated amyloid deposition in the brain parenchyma and around the cerebral vessel walls over time. These deposits were almost completely absent in control mice, including mice that received synthetic recombinant human growth factor.

"This data indicate that the vials used for human treatment indeed contained amyloid beta material that was competent to seed the accumulation of pathological amyloid," said Claudio Soto, PhD, of the University of Texas McGovern Medical School at Houston, who was not involved with the study. "This study, added to the previous one, strongly suggests that amyloid beta deposition seen in patients was induced in a manner reminiscent to prions."

More than 15 years ago, that beta-amyloid plaques were a disorder of protein folding, analogous to prion pathology, such that one misfolded amyloid protein could catalyze misfolding of others to form toxic aggregates.

The question still remains whether transmission of Alzheimer's pathology is restricted to these rare conditions -- such as the use of human-derived products for treatment -- or can occur under more common medical practices like blood transfusions, Soto told 麻豆传媒.

Concerns about transfusions have been around for some time, noted Bart De Strooper, MD, PhD, of the University College London in England. "Several studies using mice that were similarly genetically primed to develop Alzheimer's disease-like symptoms have shown that this route of transmission is theoretically possible," he told the U.K. Science Media Centre. These findings prompted a that found no evidence for increased rates of Alzheimer's or Parkinson's disease in patients who received blood from donors who went on to develop those diseases. "Those results provided real-world evidence that any such risk is extremely small," De Strooper said. "Nevertheless, it is worth monitoring these risks."

While Collinge emphasized there is no suggestion Alzheimer's disease is contagious or transmissible by blood, he noted it's important to evaluate the risks of iatrogenic transmission of amyloid beta pathology.

"We have now provided experimental evidence to support our hypothesis that amyloid beta pathology can be transmitted to people from contaminated materials," he said. "It will be important to review risks of transmission of amyloid pathology by other medical procedures still done today, including instruments used in brain surgery, drawing on other research and what we already know about accidental CJD transmission."

Mice in this study received samples injected directly into their brains, while people who received the cadaveric human growth hormone preparations decade ago had injections intravenously or intramuscularly, observed Tien-Phat Huynh, MD-PhD candidate, and David Holtzman, MD, both of Washington University in St. Louis, in an .

"Future studies in animals should assess whether the route of administration influences the ability of material containing misfolded amyloid beta to cause brain amyloid beta pathology, and should investigate the minimum amount of material that has pathological effects," they wrote.

It's worth noting that the stored vials had been maintained at ambient temperature since the mid-1980s, they added. "Their ability to transmit amyloid beta pathology seen in this study corroborates the idea that amyloid beta seeds are remarkably stable," they noted. "This property of amyloid beta seeds emphasizes the importance of not using biological material prepared from the human central nervous system for injection or transplantation into patients during neurosurgical or medical procedures, unless these materials are adequately screened or there is no other option."

The mice in this study were genetically modified to be prone to amyloid beta pathology, but not tau. The samples of human growth hormone people were exposed to also contained tau, Collinge said, and future studies will assess whether the tau in these vials can seed aggregation in other mice.