University of Manchester scientists have uncovered evidence that a build-up of a common body waste product in the brain could be helping to drive two of our most devastating neurological diseases.
In a new study, researchers found unusually high levels of urea – a waste chemical normally flushed out in urine – in the brains of people with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
The study, published in this month’s edition of the journal Molecular Omics xx and mainly funded by the Lee Trust in New Zealand, raises fresh questions about how the brain clears harmful substances.
Previous work by the same group had already shown this ‘toxic waste’ build-up in five other dementias, including Alzheimer’s and Parkinson’s-related dementia, but this is the first time it has been confirmed in FTD and ALS.
Frontotemporal dementia typically affects people under 65 at a rate of around 15.1 cases per 100,000 each year, while ALS is rarer at about 2.1 new cases per 100,000, yet both conditions are incurable and often fatal.
FTD is the second most common form of early-onset dementia and affects areas of the brain linked to behaviour and personality, while ALS attacks the nerve cells that control movement, leading to progressive muscle weakness.
Despite their differences, the two diseases are closely linked, with studies suggesting up to 15 per cent of ALS patients also develop FTD and around half show some level of cognitive problems.
Scientists also know the diseases share key biological features, but exactly what drives them remains unclear and there are still no effective treatments. the first half of your story here.
Using highly sensitive lab techniques, the team measured urea levels in different parts of the brain and compared people with the diseases to those without in people who had donated their bodies to scientific research after death.
They discovered that in people with FTD, this ‘toxic waste’ was not just in the most damaged areas but spread in both damaged areas and relatively sparred areas, while in ALS it was mainly concentrated in regions controlling movement.
The scientists say the findings suggest the brain may struggle to get rid of waste properly, potentially poisoning nerve cells over time and worsening disease.
The results add to growing evidence that the same problem has already been seen in several other conditions, hinting at a shared weakness in how the brain handles waste.
“This is exciting because it suggests we might be looking at a common problem underlying several different brain diseases, rather than separate conditions with completely different causes,” said Dr Sasha Philbert, the study’s lead author from The University of Manchester.
He added: “If we can work out why this waste is building up and how to clear it, we may be able to slow or even stop these diseases, opening the door to new treatments for conditions that currently have very few options.”
- The paper Elevated urea levels in human frontotemporal dementia and amyotrophic lateral sclerosis post-mortem brain tissue: evidence of a multi-dementia pathogenic mechanism is published in Molecular Omics, https://doi.org/10.1093/molecular-omics/aaiag019
