A gradual loss of blood flow to the brain over years or decades could be a major trigger for Alzheimer's disease, according to a study to be published Friday.
Up to now, what provokes the debilitating disease has remained a mystery, even if the mechanism causing the damage is well understood.
The new research shows that an insufficient supply of sugar glucose, transported by blood, sets off a biochemical chain reaction resulting in the accumulation of the neuron-attacking proteins that cause Alzheimer's.
"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," said Robert Vassar, a professor at Northwestern University's Feinberg School of Medicine, and lead author of the study.
Exercising, reducing cholesterol intake, and managing hypertension are all measures that could provide added protection, he said.
"If people start early enough, maybe they can dodge the bullet," Vassar said in a statement.
And for persons who already show symptoms of constricted arteries, taking vasodilators -- drugs that boost blood flow -- could help deliver nourishing oxygen and glucose to the brain.
Drawing from experiments with humans and mice, Vassar and colleagues showed that reduced blood flow alters a protein called elF2alpha.
In its changed form, elF2alpha increases the output of the enzyme that spurs production of the fiber-like knots of amyloid beta protein that form outside neurons and disrupt their ability to send messages.
Vassar discovered the key role of the enzyme, BACE1, in promoting Alzheimer's a decade ago.
The new study opens a path to the development of drugs designed to block elF2alpha, and thus the biochemical process leading to the disease, he said.
It also suggests that Alzheimer's may result from the same type of energy deprivation that occurs in a stroke.
Rather than dying, the brain cells react by increasing the BACE1 enzyme, which offers short-term protection but is harmful in the long run.
"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event," he explained. "What we are talking about here is a slow, invidious process over many years where people have a low level of cardiovascular disease."
"It is so mild, they don't even notice it, but it has an effect over time because it is producing a chronic reduction in the blood flow," he added.
Alzheimer's is a degenerative disorder of the brain characterised by forgetfulness and dementia.
It is caused by a massive loss of cells in several regions of the brain, driven by a buildup of plaques of amyloid protein.
The disease occurs most frequently in old age, but some genetic variants have been shown to increase risk as well.
The number of people worldwide afflicted with the disease is set to rise from 24 million people today to 42 million in 2020 and 81 million in 2040, according to the World Health Organisation.
The study is to be published in the December 26 issue of Neuron, a journal based in Cambridge, Massachusetts.