Theory of amyloid-β ‘transmissibility’ gains traction

Written by Sharon Salt, Editor

In 2015, a study was published in Nature that indicated that growth hormones given to children decades ago seem to have spread proteins linked to Alzheimer’s disease. Investigators reported that amyloid-β deposits were present in autopsies of individuals with Creutzfeldt–Jakob disease who had received injections of human growth hormone extracted from dead bodies that were contaminated by prions.
This finding led to the first evidence that Alzheimer’s could possibly be transmitted from one person to another.

With various hypotheses for this floating around, the research team went on to further identify and biochemically analyze vials of the cadaver-derived growth hormone. This has led to the publication of a more recent study, also in Nature, which illustrates that sticky proteins associated with neurodegenerative diseases may be transferred in mice.

Within their study, the researchers revealed that all individuals receiving the growth hormone extracted from cadavers used one particular extraction method (method A). They then compared growth hormone extracted in this way with three other methods (methods B, C and D) and demonstrated that amyloid-β and tau proteins were only present in samples using extraction method A.

Thus, to identify if this exposure to Alzheimer’s proteins could be enough to seed later disease, the investigators went on to examine whether injecting archived human growth hormone into the brains of genetically engineered mice would make them develop some form of human-like disease pathology for Alzheimer’s.

The results of their recent study illustrated that these mice went on to accumulate amyloid-β and tau proteins in their brains. In addition to this, mice that were injected with brain tissue from individuals with Alzheimer’s also had accumulation of these proteins. However, control mice that were injected with synthetic growth hormone showed no signs of amyloid-β or tau proteins.

You might also like:

Although the publication adds traction to the ‘transmissible’ theory of Alzheimer’s, the researchers have cautioned that the risks for humans are likely to be minimal. They have also stressed that their research does not suggest that disorders such as Alzheimer’s are contagious, but instead, raises concerns that certain medical and surgical procedures pose a risk of transmitting such proteins between humans, which may lead to brain disease later.

Bart De Strooper and Adrian Ivinson, Directors of the UK Dementia Research Institute (University College London, UK), commented: “It is important to recognize that the experimental design described in the new work very much favors the chance that such amyloid transmission will be observed. Extracts from pooled brains were directly injected in the brains of mice that were genetically modified to develop amyloid plaques” [1].

They concluded that: “The fact that no seeding was observed after injecting the same material into wild-type (normal) mice means we should be very cautious about extrapolating the conclusions to real-life conditions. Transmissibility of amyloid is clearly very low, and will therefore occur only under exceptional conditions in human beings. The treatment of patients with human brain extracts is obviously one such exceptional condition and was ended more than 30 years ago precisely to avoid this problem” [1].


Source: Purro SA, Farrow MA, Linehan J et al. Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone. Nature doi:10.1038/s41586-018-0790-7 (2018) (Epub ahead of print).

Reference:
[1] UK Dementia Research Institute.
https://ukdri.ac.uk/news-and-events/comment-transmission-of-amyloid-beta-pathology
[Accessed 14 December 2018]