Less oxygenated blood to the brain may mean a bigger build-up of the protein plaques that are so closely tied to Alzheimer’s disease, new research shows.
The Canadian team says a specific gene may be key to this process.
"If you have less oxygen, you turn up this gene and obviously generate more beta-amyloid [protein]. If you have a higher level of beta-amyloid, you form more plaque. If you have this plaque, then you will have dementia," explained lead researcher Weihong Song, a professor of psychiatry who holds a Canada Research Chair in Alzheimer’s disease at the University of British Columbia in Vancouver.
His team described the findings in this week’s issue of theProceedings of the National Academy of Sciences.
Experts have long known that lowered brain-oxygen levels, caused by reduced blood flow, increase the risk of Alzheimer’s disease. For example, Song said, "If you have a stroke, you have a two or three times increased risk of dementia."
The link between low oxygen and plaque formation may be a gene called BACE 1, he added. This gene encodes a protein that converts the precursor amyloid molecule to the more dangerous beta-amyloid form.
In their studies with mice, Song’s group found that lower oxygen levels increased the activity of the gene.
But its not quite that simple, added Dr. Ralph A Nixon, professor of psychiatry and cell biology at New York University and a spokesman for the Alzheimer’s Association.
To start with, there is an ongoing debate about whether the amyloid plaques cause the loss of mental function seen in Alzheimer’s disease, Nixon said.
"What this paper does is add to a hypothesis that relates to amyloid overproduction and accumulation in the brain," he said. "Whether it establishes an association is the issue."
Hypoxia — low blood-oxygen levels — "does a lot of things to the brain," Nixon said. "It has a lot of effects on brain function other than what is being described here. There should be at least some consideration of the broader context — that hypoxia itself is a cause of impairment."
Nevertheless, Nixon said, the report "is an interesting additional link that has not been appreciated before between hypoxia and this metabolic pathway."
Nixon and Song did agree on one point.
"The study reinforces another message that has emerged in recent years — that the health of the cardiovascular system is very important for the health of the brain," Nixon said. "The things one does to promote the health of the cardiovascular system are going to help the brain when it is challenged in Alzheimer’s disease. Lifestyle factors such as diet and exercise are also an edge against hypoxia."
Song concurred. "If we can improve blood flow to the brain, maybe we can help slow Alzheimer’s progression. This report provides the mechanics for that. Increasing blood flow for the heart also helps slow Alzheimer’s disease," he said.
