The build-up of urea, also known as carbamide, in the brain to toxic levels can cause brain damage — and eventually dementia, according to new research.
An old man diagnosed as suffering from senile dementia. Color lithograph, 1896, J. Williamson, Byrom Bramwell. Image credit: Wellcome Images / CC BY 4.0.
Published in the Proceedings of the National Academy of Sciences, the study shows that the neurodegenerative disorder Huntington’s Disease — one of seven major types of age-related dementia — is directly linked to brain urea levels and metabolic processes.
“Our 2016 study revealing that urea is similarly linked to Alzheimer’s, shows that the discovery could be relevant to all types of age-related dementias,” said co-author Professor Garth Cooper, from the University of Manchester, UK.
“The Huntington’s study also showed that the high urea levels occurred before dementia sets in, which could help doctors to one day diagnose and even treat dementia, well in advance of its onset.”
Urea is more commonly known as a compound which is excreted from the body in urine.
Urea and ammonia in the brain are metabolic breakdown products of protein. If they build up in the body because the kidneys are unable to eliminate them, for example, serious symptoms can result.
“This study on Huntington’s Disease is the final piece of the jigsaw which leads us to conclude that high brain urea plays a pivotal role in dementia,” Professor Cooper said.
“Alzheimer’s and Huntington’s are at opposite ends of the dementia spectrum — so if this holds true for these types, then I believe it is highly likely it will hold true for all the major age-related dementias.”
“More research, however, is needed to discover the source of the elevated urea in Huntington’s Disease, particularly concerning the potential involvement of ammonia and a systemic metabolic defect.”
“This could have profound implications for our fundamental understanding of the molecular basis of dementia, and its treatability, including the potential use of therapies already in use for disorders with systemic urea phenotypes.”
The researchers used cutting-edge gas chromatography mass spectrometry to measure urea levels in human brains as well as in the brains of transgenic sheep in Australia.
“For levels to be toxic urea must rise 4-fold or higher than in the normal brain,” Professor Cooper said.
“We already know Huntington’s Disease is an illness caused by a faulty gene in our DNA — but until now we didn’t understand how that causes brain damage — so we feel this is an important milestone.”
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Renee R. Handley et al. Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases. PNAS, published online December 11, 2017; doi: 10.1073/pnas.1711243115
