Toxic build-up of urea in the brain major cause of dementia: study

The build-up of urea in the brain to toxic levels can lead to brain damage and eventually dementia, according to a study that confirms the major cause of the neurodegenerative disease.

The finding has important implications for possible treatment and diagnosis of dementia, according to Professor Garth Cooper from The University of Manchester in the UK.

The work follows on from Cooper's earlier studies, which identified metabolic linkages between Huntington's, other neurodegenerative diseases and type-2 diabetes.

The study, published in the journal PNAS, shows that Huntington's Disease - one of seven major types of age- related dementia - is directly linked to brain urea levels and metabolic processes.

Their previous study revealing that urea is similarly linked to Alzheimer's, shows that the discovery could be relevant to all types of age-related dementias.

The Huntington's study also showed that the high urea levels occurred before dementia sets in, which could help doctors to diagnose and even treat dementia, well in advance of its onset.

Urea and ammonia in the brain are metabolic breakdown products of protein.

Urea is more commonly known as a compound which is excreted from the body in urine. If urea and ammonia 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," said Cooper.

"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," said Cooper.

"More research, however, is needed to discover the source of the elevated urea in HD, particularly concerning the potential involvement of ammonia and a systemic metabolic defect, he said.

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, researchers said.

Dementia results in a progressive and irreversible loss of nerve cells and brain functioning, causing loss of memory and cognitive impairments affecting the ability to learn. Currently, there is no cure, researchers said.

The team used human brains, donated by families for medical research, as well as transgenic sheep in Australia, they said.