FOR decades, science has believed that Bovine Spongiform Encephalopathy (BSE) in cattle is caused by either ingesting nervous system material from by-products from infected animals, or via a rare ‘spontaneous’ form.
Now new research out of the University of Alberta in Canada is throwing light on other possible sources of infection.
Recent research led by the University of Alberta challenges the belief that BSE 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, published in the International Journal of Molecular Sciences, 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 multi-faceted process behind that neurodegeneration, showing that inflammation weakens the brain’s defenses 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,” Dr Ametaj said.
New clue to a devastating outbreak
The discovery suggests that endotoxins in the animal-derived feed offered to cattle may have contributed to the BSE crisis in the United Kingdom, he said.
The outbreaks devastated the livestock industry in the 1980s and 1990s, resulting in the deaths of 160 people who had 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 40pc 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 50pc.
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 worsened damage to the brain, resulting in 100pc mortality within 200 days of infection.
The new findings could offer insight into why there were many more BSE cases in England and Wales than in Scotland, based on the procedures rendering plants used to make livestock feed, Dr Ametaj said.
“Rendering plants in England and Wales removed a critical substance called hexane from the production process to cut costs. This solvent was essential not only for fat extraction, but also for dissolving and removing LPS from the meat-and-bone meal.
“In contrast, Scottish rendering plants retained the hexane step and, potentially because of that, had markedly fewer BSE cases—a fact long known but never systematically explained,” he noted.
The study measured LPS in meat-and-bone meal – the feed implicated in BSE- blood meal and tallow, and confirmed high levels of contamination.
Combined with chronic exposure to such feed, predisposing conditions in dairy cows induced by high-grain diets immediately postpartum, and by an increased “leaky gut,” can trigger systemic inflammation and could contribute to the development of neurodegenerative disease, Dr Ametaj noted.
“This suggests that excluding the hexane step left contaminated feed that could independently trigger neuro-degeneration, explaining why the BSE epidemic followed the geographic pattern it did,” he said.
Implications for human diseases
The research may hold major implications for feed and livestock producers.
“The lessons from the BSE outbreaks about proper rendering processes and better feed safety remain relevant today. The prevention path is clear: maintain endotoxin-removal processing steps and monitor contamination. Any industrial feeding system that doesn’t control this could create conditions for neurodegeneration,” Dr Ametaj said.
He is also “cautiously optimistic” about how the findings could help prevent or treat human diseases such as Alzheimer’s and Parkinson’s.
“It opens up an entire anti-inflammatory medicine toolkit. Bacterial endotoxins have been found in the brains of Alzheimer’s patients, so risk factors that reduce dementia – exercise, anti-inflammatory diets, gut health, metabolic health—might work partly by reducing endotoxin burden.”
“These diseases are complex, but if endotoxin exposure contributes to even 20-30pc of cases, controlling this modifiable risk factor could spare millions of people,” Dr Ametaj said.
“We might prevent some neuro-degenerative diseases the way we prevent heart disease, by managing inflammatory risk factors throughout life. In a field where there’s been little hope, that matters.”
Source: University of Alberta