New Research Suggests Mad Cow Disease May Have Been Triggered by More Than Misfolded Proteins
For decades, mad cow disease bovine spongiform encephalopathy (BSE) has been blamed almost exclusively on misfolded infectious proteins known as prions. But groundbreaking research led by the University of Alberta is challenging that long-standing theory and shedding new light on why the devastating outbreaks in the U.K. unfolded the way they did.
The new study, led by Burim Ametaj, a nutritional immunobiologist in the Faculty of Agricultural, Life & Environmental Sciences, reveals something never previously demonstrated: prion-like neurodegeneration can occur even without infectious prions.
A New Suspect: Bacterial Endotoxin
The research points to a powerful bacterial endotoxin lipopolysaccharide (LPS) as a key player capable of triggering the same kind of brain damage seen in prion diseases.
Ametaj explains that the findings overturn traditional assumptions:
“This fundamentally challenges the prevailing theory that these types of brain diseases are only about prions or similar misfolded proteins.”
Instead, the team found that chronic inflammation caused by LPS weakens the brain’s defenses, overwhelms cells, and sets the stage for protein misfolding and immune-driven damage. These processes feed each other, creating a destructive cycle.
Connecting the Dots to the U.K.’s BSE Disaster
The discovery adds a compelling new layer to one of the biggest agricultural crises in history. In the 1980s and 90s, BSE spread through the U.K., leading to:
the deaths of more than 160 people
the slaughter of more than four million cattle
Ametaj’s research suggests that endotoxin contamination in cattle feed may have played a major role — independent of the prion responsible for BSE.
Mouse models in the study developed spongiform brain damage (“holey” tissue similar to BSE) in:
40% of cases when exposed to LPS alone
50% when exposed to LPS plus misfolded proteins
100% mortality when LPS exposure occurred alongside actual prion infection
The results are striking: damaging neurodegeneration occurred even without infectious prions present.
Why England and Wales Suffered More Than Scotland
The research also offers a possible explanation for a long-observed mystery: why BSE cases were dramatically higher in England and Wales than in Scotland.
According to Ametaj, rendering plants in England and Wales removed a solvent called hexane to reduce production costs. Hexane was used not only to extract fat but also to dissolve and remove endotoxins like LPS from meat-and-bone meal.
Scottish plants kept the hexane step — and saw far fewer BSE cases.
The team measured LPS levels in several feed ingredients implicated in BSE, including meat-and-bone meal, blood meal, and tallow, confirming high contamination.
Combined with factors like high-grain diets that promote “leaky gut” and systemic inflammation, the picture becomes clearer:
Skipping the hexane step may have left behind feed capable of triggering neurodegeneration on its own.
Implications for Today — and for Human Health
The findings have major significance for livestock producers, feed manufacturers, and regulators.
Ametaj emphasizes the need to maintain processing steps that remove endotoxins and to closely monitor contamination levels:
“Any industrial feeding system that doesn’t control this could create conditions for neurodegeneration.”
The research also raises hope for human medicine. Bacterial endotoxins have been found in the brains of people with Alzheimer’s, and the new data suggest anti-inflammatory strategies may play a role in reducing risk.
Exercise, gut health, metabolic health, and anti-inflammatory diets may help reduce endotoxin burden — potentially influencing diseases like Alzheimer’s and Parkinson’s.
As Ametaj puts it, “In a field where there’s been little hope, that matters.”
The study involved collaborators from the University of Alberta, the University of Warmia and Mazury in Poland, and several graduate students and postdoctoral fellows. It was funded by the former Alberta Livestock and Meat Agency and the Alberta Prion Research Institute.
