Unfortunately, it’s time to talk transmissible protein pathology again. That’s the unnerving idea that misfolded proteins can, under some conditions, act as infectious agents (prions are the most famous examples and the most widely-used name for these). I wrote in 2015 about a particularly alarming possibility. It’s known that up until the 1980s, some patients who had been treated with human-cadaver-isolated growth hormone preparations had also been infected with the prion that causes Creutzfeld-Jacob disease. The 2015 paper saw signs of amyloid pathology as well, and suggested that misfolded amyloid protein had been transmitted, too.
Now the authors appear to have nailed that down. They’ve tracked down archived vials of the growth hormone in England, and they’ve shown that these contain beta-amyloid (both 40 and 42 amino acid length) as well as tau protein. And what’s more, they did experiments with mice expressing humanized APP and mutations that are known to produce amyloid pathology. It’s already known that inoculation with brain homogenate from human Alzheimer’s patients seeds amyloid plaque formation. But inoculation with these old HGH samples is sufficient to induce amyloid pathology as well. The results seem very clear. Animals treated by intracerebral injection with saline or with recombinant growth hormone look just like untreated controls, but every one of the old-growth-hormone treated animals show both plaques out in the neurons and along the vasculature (cerebral amyloid angiopathy).
Our proposal that human transmission of Aβ pathology had occurred as a result of intramuscular injection of c-hGH is now firmly supported by experimental evidence. While the individuals we described in our earlier report did not meet the full neuropathological criteria for Alzheimer’s disease, they might have done so if they had not died of iCJD at a relatively young age.
Coupled with the news that amyloid pathology has been spread through surgical procedures (mentioned in that earlier blog post as well) and with other experiments on spreading amyloid deposits, it seems past time to start being careful about this business.
Although we reiterate that there is no suggestion that Alzheimer’s disease is contagious, and no supportive evidence from epidemiological studies that it is transmissible (notably by blood transfusion), we consider it important to evaluate the risks of iatrogenic transmission of CAA, and potentially of Alzheimer’s disease. Given the lack of disease-modifying therapeutics for Alzheimer’s disease and other distressing and fatal neurodegenerative conditions, it will be important to consider introducing improved methods for removing proteopathic seeds from surgical instruments on a precautionary basis.
That it is. And I’m not sure what those improved methods will look like, considering how resistant some of these protein aggregates can be. But there seems no doubt that under forcing conditions (direct injection of protein or tissue preparations, transmission by surgical procedures, etc.) that these pathologies can be transmitted. This along with the work on alpha-synuclein and other such proteins tells us that we really can be living on the edge when it comes to protein stability. You’d think that the danger would be instability – after all, things fall apart. But there is such a thing as too much stability. Life needs to be flexible and to take advantage of reversible reactions, so thermodynamic sinkholes like these protein aggregates are as deadly as a tar pit.