Groundbreaking research led by the University of Alberta challenges the belief that mad cow disease is caused only by misfolded proteins — a discovery that sheds new light on the devastating outbreak in the United Kingdom 40 years ago and provides new hope for prevention.
The study shows for the first time that such prion-like brain diseases can be triggered without the presence of infectious prions. Prion disease occurs when normal proteins in the brain misfold into infectious, abnormal proteins.
Instead, chronic inflammation caused by a powerful bacterial endotoxin called lipopolysaccharide (LPS) was identified as a culprit that can independently trigger brain damage resembling prion disease.
"This fundamentally challenges the prevailing theory that these types of brain diseases are only about prions or similar misfolded proteins," says Burim Ametaj, a nutritional immunobiologist in the Faculty of Agricultural, Life & Environmental Sciences and lead author on the study.
The research revealed more of a multifaceted process behind that neurodegeneration, showing that inflammation weakens the brain's defences first, overwhelming cells. Proteins could then start misfolding and the immune system over-reacts, causing more damage.
"All three processes feed into each other, which means we need to target inflammation and immune health, not just the misfolded proteins."
New clue to a devastating outbreak
The discovery suggests that endotoxins in the animal-derived feed offered to cattle may have contributed to the bovine spongiform encephalopathy (BSE), or mad cow disease, crises in the United Kingdom, Ametaj says.
The outbreaks devastated the livestock industry in the 1980s and 1990s, resulting in the deaths of more than 160 people who'd eaten infected beef, and the slaughter of more than four million cattle.
The study provided striking evidence that LPS alone, administered under the skin, caused spongiform brain symptoms in 40 per cent of mouse models — a "holey" appearance in the tissues seen in BSE and related diseases. When LPS was combined with lab-created misfolded proteins, that number rose to 50 per cent. In both scenarios, this Alzheimer-like damage happened even when the naturally occurring infectious prion responsible for BSE was absent.
The research also showed that when an actual prion disease such as BSE is present, inflammation caused by LPS dramatically worsens damage to the brain, resulting in 100 per cent mortality within 200 days of infection.
