An international team of scientists, consisting of experts from the University of Manchester, the University of Auckland, AgResearch New Zealand, the South Australian Research and Development Institute, Massachusetts General Hospital and Harvard University, has confirmed the discovery of the main cause of dementia, which will have important implications for its possible treatment and diagnosis.
According to lead researcher Garth Cooper from the University of Manchester (UK), the build-up of urea in the brain to toxic levels can cause brain damage and eventually dementia.
It is a continuation of Cooper’s earlier studies, which identified metabolic links between Huntington’s disease, other neurodegenerative diseases, and type 2 diabetes.
The study shows that Huntington’s disease, one of the seven main types of age-related dementia, is directly associated with brain urea levels and metabolic processes.
The scientists used state-of-the-art gas chromatography and mass spectrometry to measure brain urea levels. For levels to be toxic, urea must rise 4 times or more, relative to normal brain levels.
Their 2016 study, which reveals that urea is similarly linked with Alzheimer’s is evidence, according to Cooper, that this finding could be relevant for all age-related types of dementia.
They also found that high urea levels occurred before dementia started , which could help doctors diagnose and even treat dementia long, long before it started.
The team used human brains, donated for medical research by various families, as well as transgenic sheep in Australia.
Unraveling dementia
Urea and ammonia – in the brain – are metabolic breakdown products. Urea is more commonly known as a compound that is excreted from the body in the form of urine. If urea and ammonia build up in the body because the kidneys cannot remove them, for example, severe symptoms can appear.
“ This Huntington’s disease study is the final piece of the puzzle leading us to conclude that elevated brain urea plays a critical role in dementia. However, more research is needed to discover the source of elevated urea in the disease. Huntington’s disease, particularly with regard to the possible involvement of ammonia and a systemic metabolic defect, “Cooper explains to the journal PNAS.
Dementia causes a progressive and irreversible loss of nerve cells and brain function, causing memory loss and cognitive deficits that affect learning ability. Currently, there is no cure.
“We already know that Huntington’s disease is a disease caused by a defective gene in our DNA, but until now we did not understand how that caused brain damage, so we believe it is an important milestone,” Cooper concludes.
Referencia: Renee R. Handley el al., “Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases,” PNAS (2017). www.pnas.org/cgi/doi/10.1073/pnas.1711243115
