Summary: A new study by Northwestern University researchers details the biochemistry of how reduced blood flow to aging brains might contribute to Alzheimer’s. Regular exercise is the best way to improve that blood flow.
Have you made a New Year’s resolution to improve your diet and exercise? If so, it might reduce your risk of Alzheimer’s. A growing number of studies link lifestyle factors such as poor diet and lack of exercise to dementia, but it’s unclear exactly how these factors might contribute to the plaques and tangles some researchers think are responsible for the disease.
Robert Vassar, Ph.D.
A new study by Dr. Robert Vassar and his colleagues at Northwestern University sheds light on one mechanism by which lifestyle might contribute to Alzheimer’s pathology. They conducted a complex series of experiments to show that reducing the amount of glucose available to brain cells sets off a chain reaction that increases beta amyloid, the protein involved in Alzheimer’s plaques.
Glucose is the sugar your body makes from the food you eat. It circulates through the bloodstream, providing fuel for cells. Previous studies have linked reduced processing of glucose in the brain [seen on PET scans] to Alzheimer’s.
Dr. Vassar and colleagues had already shown that decreasing the amount of glucose available to brain cells increases the level of beta secretase (BACE), an enzyme involved in the formation of beta amyloid.
Their new study adds some detail about this process, showing that a protein called eIF2alpha-P changes when cells are deprived of glucose, and that this results in the increase in BACE, causing an increase in beta amyloid. They observed this chain reaction in cell cultures, in mice genetically engineered to develop Alzheimer’s, and in brain cells of people who were diagnosed with Alzheimer’s before they died.
It’s unlikely that glucose deprivation is the one thing that kicks off the chain of events leading to Alzheimer’s. “My guess is that many types of age-related physiological stresses could increase eIF2alpha-P and BACE,” says Dr. Vassar. “Hence, there are probably multiple factors that could lead to Alzheimer’s. Some of these, like reduced glucose and oxygen, could act together in an additive way to make matters worse.”
It appears that decreased blood flow to the brain is responsible for lowering the amount of glucose (and oxygen) getting to the brain. “We think that during aging, a mild, low-level reduction in blood flow to the brain occurs over the years, perhaps decades, that it takes for Alzheimer’s to develop,” he explains. “It’s probably at a level that goes unnoticed by the individual until dementia sets in. The reduced blood flow might be the result of atherosclerosis [hardening of the arteries] and cardiovascular disease.”
It’s interesting that changes in eIF2alpha-P are also seen in people with brain injuries and hardening of the arteries (risk factors for dementia), and in those with other brain disorders such as Parkinson’s disease, Huntington’s disease, and ALS. Understanding the role of this protein in Alzheimer’s and other diseases could lead to development of new drugs, but that would take years.
So for now, increasing blood flow to the brain through cardiovascular exercise is the best option for improving glucose levels. Although eating more sugar might temporarily increase glucose in the blood, it would also promote weight gain and diabetes. “I favor the idea of prevention through regular cardiovascular exercise starting at least by middle age,” says Dr. Vassar, “and through reduced cholesterol in the diet and management of weight, high cholesterol and hypertension if necessary.”
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