Media ReleaseFrom: Springer Nature
Neurodegeneration: Further evidence for the transmission of amyloid beta pathology (N&V) *PRESS BRIEFING*
Specific batches of cadaveric human growth hormone (c-hGH) samples were contaminated with amyloid beta protein, reports a paper published online in Nature this week. These samples were able to subsequently seed amyloid beta pathology in mice. A previous paper suggested c-hGH as a possible source of amyloid beta pathology in four patients that had received c-hGH as treatment for short stature. Although these new findings do not demonstrate the direct transmission of Alzheimer’s disease, they provide experimental evidence that the c-hGH the patients received is able to transmit amyloid beta pathology.
A Nature paper published in 2015 reported the presence of amyloid beta pathology in the brains of four out of eight patients who had received prion-contaminated c-hGH and subsequently died of Creutzfeldt–Jakob disease (CJD). Amyloid beta pathology is a hallmark of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease. Several of the patients displayed pathology resembling CAA; however, none met the full neuropathological criteria for Alzheimer’s disease. Although the human transmission of CJD as a result of certain medical procedures (iatrogenic transmission) had been previously documented, this study suggested that the patients may have developed amyloid beta pathology from the treatment with c-hGH. However, further investigation was required to determine whether the c-hGH samples were contaminated with amyloid beta.
Following on from this previous work, John Collinge and colleagues obtained several of the c-hGH samples that the patients had been exposed to. These were analysed biochemically for the presence of amyloid beta and tau protein, and a number of samples tested positive for both.
Next, the authors investigated whether the amyloid beta protein found in the samples had the potential to seed amyloid beta pathology in live organisms. c-hGH samples were administered to genetically modified mice, which express a mutated, humanized version of the amyloid precursor protein (APP) gene and develop the first signs of amyloid beta deposition at around six months of age. Female mice aged 6–8 weeks received injections of the original c-hGH samples directly into the brain. At 240 days post-injection, amyloid beta deposits and CAA were consistently found in mice that received the original c-hGH samples, but were almost completely absent in various control mice (including those that received currently used synthetic recombinant hGH). The authors highlight that the seeding potential of the tau detected in the c-HGH samples requires testing in a separate tau mouse model.
These findings demonstrate that the original c-hGH batches contained amyloid beta that is able to seed amyloid beta pathology in mice, and provides experimental evidence to support the hypothesis that amyloid beta pathology can be transmitted to humans by iatrogenic means. The authors emphasize that there is no suggestion that Alzheimer’s disease is a contagious disease or transmissible by blood transfusion, although they state that it is important to evaluate the risks of iatrogenic transmission of amyloid pathologies.
**Please note that a telephone press briefing will take place UNDER STRICT EMBARGO on Wednesday 12 December at 1500 London time (GMT) / 1000 US Eastern Time.**
Author John Collinge will discuss the research. This will be followed by a Q&A session.
To attend this briefing you will need to pre-register by following the link here. Once you are registered, you will receive an email containing the dial-in details for the conference. You will also be provided with the option to save the details of the briefing to your calendar.