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 new study.
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 suggests 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
"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.
Dodging the bullet
"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 fibre-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.
Similar to stroke
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
"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, insidious 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
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 build-up 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 was published in the December 26 issue of the journal Neuron.
(Sapa-AFP, December 2008)