AsianScientist (Jan. 25, 2016) – One cow stumbles around as its rear legs collapse repeatedly. Another cow behaves uncharacteristically aggressively, kicking violently when contained in a pen. Images like these were widely shown on television during the early ’90s at the peak of the bovine spongiform encephalopathy (BSE) scare, more commonly known as ‘mad cow disease.’
But more frightening still were reports of people who contracted the human form—called variant Creutzfeld-Jakob disease (vCJD)—by eating contaminated beef. Decades later, the fear associated with prion diseases, the category that BSE and vCJD belong to, continues to loom at the back of the public’s mind.
Proteins as infectious agents
Characterized by holes in the brain that lead to a spongy appearance, prion diseases include the human disease kuru, which was transmitted by cannibalism among the Fore people of Papua New Guinea, and scrapie in sheep.
In 1982, Professor Stanley Prusiner from the Department of Neurology at the University of California, San Francisco, identified the cause of scrapie as being a protein that appeared to be infectious, and invented the term prion, short for ‘proteinaceous infectious particle.’
But his peers were initially skeptical as it was common belief then that scrapie and vCJD were caused by a virus. Prusiner eventually won the 1997 Nobel Prize in Physiology or Medicine for showing that these diseases were indeed caused by protein aggregates.
Thirty-three years later, he’s added a new chapter to the story. In August 2015, Prusiner published a paper in the Proceedings of the National Academy of Sciences showing that, in mice at least, prions are behind yet another neurodegenerative disease: multiple system atrophy (MSA).
Similarities of MSA to Parkinson’s disease, such as aggregations of alpha-synuclein protein, mean it is often misdiagnosed as the latter. The authors even suggest the possibility of accidental transmission via surgical instruments, given the knowledge of prion resistance to standard sterilization treatments.
While the media mulled over a new prion disease, researchers in the UK published their findings in Nature describing a group of people that contracted vCJD after being treated with contaminated human growth hormone. The patients showed evidence of amyloid beta (Aβ) protein aggregates, which are characteristic of Alzheimer’s disease.
While some of these reports urged caution in the interpretation of the results, others pondered whether people would delay or cancel surgery. As the study also stressed vigilance when dealing with surgery involving neurological tissue, is someone who had a root canal surgery at risk of developing Alzheimer’s or Parkinson’s disease?
Aβ: Not quite the smoking gun
Professor Andrew Hill, who conducts research into prion diseases at LaTrobe University in Australia, and Dr. Andrea Lim, a research fellow examining Alzheimer’s disease at the National University of Singapore, think not.
“While abnormal protein aggregation is a feature of Parkinson’s and Alzheimer’s disease, this does not automatically make them prion diseases as they do not always transmit a disease phenotype,” says Hill. This aspect is particularly crucial to Alzheimer’s disease, which is also characterized by cognitive decline and tangles in a protein called tau (Ʈ), in addition to Aβ.
“The presence of tau tangles in Alzheimer’s is important because they correlate with disease progression,” explains Lim. “It is possible to have amyloid deposits in the brain but be cognitively normal.”
Accordingly, none of the vCJD patients who received contaminated human growth hormone showed tau pathology, and it is not known if memory tests had been performed.
Regarding the MSA study, Hill points out that MSA neurodegeneration was induced in genetically-engineered mice expressing amutant form of alpha-synuclein.
“They have shown a theoretical possibility that MSA could be a prion disease,” he says. “The authors raise potential issues of neurosurgical instruments representing a biocontainment risk but this would be mitigated if using disposable equipment.”
The proof is in the tissue
While both Lim and Hill agree that it is plausible that protein aggregates could be introduced from donor tissue, there is no direct proof that this arose from the contaminated treatment.
Hill is unambiguous on the topic, “There is no clear evidence that Alzheimer’s or Parkinson’s is transmissible in the same way that prion diseases such as vCJD are.”
Even the authors of the Nature publication noted no epidemiological studies supporting transmission. So does this mean that the media overstated how afraid we should be? Not necessarily.
“The MSA paper reveals a potentially new transmissible prion disease that may widen the scope of this group of diseases,” comments Hill, “and it would be important to look at other cohorts of vCJD patients to determine the frequency in which the Aβ observation is seen.”
Ultimately, no one wants to be accidentally infected with an incurable disease, especially one with as exotic and gruesome a history as prion diseases. While Prusiner’s lab is collaborating with Japanese pharmaceutical company Daiichi Sankyo to develop diagnostics and therapies for prion diseases, there are currently no treatments available.
But until a conclusive link is made, rest assured that Alzheimer’s disease is not contagious, and yes, you should visit your grandparents this weekend.
This article was first published in the print version of Asian Scientist Magazine, January 2016.
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Photo: Shutterstock.
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