Alzheimer's disease could be caused by a failure of the brain to clear away a waste product of normal metabolism fast enough, researchers have found. This leads to a buildup of the waste and the growth of plaques that can degrade brain cells and cause damage.
Of the roughly 750,000 people in the UK who have a form of dementia, more than half have Alzheimer's disease. According to the Alzheimer's Society, in 15 years a million people will be living with dementia and this figure will rise to 1.7 million people by 2051.
The disease is caused by a build-up of plaques in the brain, made of a protein called amyloid-beta, which is a product of normal metabolism. One of the ways the brain clears away the amyloid-beta is to dump it into the spinal fluid for later disposal. A drop in levels of amyloid-beta in spinal fluid could, therefore, be an early indicator that someone will go on to develop Alzheimer's disease, perhaps because the waste protein cannot be removed from the brain and is beginning to accumulate.
To test how quickly the brain can get rid of this waste protein, Randall Bateman, an assistant professor of neurology at Washington University School of Medicine in St Louis, monitored the spinal fluid of 12 people with Alzheimer's disease over a 36-hour period and compared it to that of 12 cognitively normal individuals. He found that both sets of people were producing amyloid-beta in their brains at the same average rate, but the protein clearance rate was 30% lower on average in the group with Alzheimer's.
In a paper published today in Science, Bateman calculated that it would take 10 years for this decreased clearance to cause the build-up of amyloid-beta that is normally seen in the brains of Alzheimer's patients.
"This exciting study gives us an insight into the building blocks of Alzheimer's disease. It could be that people's natural 'rubbish trucks' are on strike and are not clearing away a protein called amyloid. We now need further research to find out why the system is not working properly and whether amyloid is toxic in higher concentrations," said Clive Ballard, director of research at the Alzheimer's Society. "The burning question is whether this process starts before the onset of symptoms, as this could be vital to the development of new treatments. As the number of people with dementia reaches a million in just 15 years we urgently need more investment in research."
Randall said the finding could have implications for diagnosis and treatment of the disease, even before symptoms developed. In the experiment, for example, some healthy subjects had lower clearance rates than average for their group, close to or slightly within the range seen in Alzheimer's patients. "Cognitive tests show no signs of dementia in these participants now, but we'll be interested to see if a lower clearance rate is a predictive marker for future diagnosis of Alzheimer's disease," said Bateman.