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Is low oxygen level in the brain a characteristic of Alzheimer's and could it be treated by a FDA approved drug?
Eugenio Gutiérrez Jiménez
University of Aarhus
Aarhus, Denmark
Background
People with cardiovascular risk factors are at an increased risk for cognitive decline as they age and may be at an increased risk for dementia. The exact cause of this relationship is unclear, although inadequate blood flow can lead to damaged cells and eventually to their death. The brain acts as a host to one of the body's richest network of blood vessels and is especially vulnerable. Changes to the brain blood vessels often coexist with changes that are linked to other types of dementia, including Alzheimer's.
Dr. Eugenio Gutiérrez Jiménez and colleagues propose to investigate whether blood flow changes in tiny brain blood vessels called capillaries, could be a characteristic of Alzheimer's.
In preliminary studies with aged and genetically engineered Alzheimer's-like mice, Dr. Jiménez and colleagues examined blood flow changes in tiny brain blood vessels called capillaries. They used a brain scan (Magnetic Resonance Imaging) technique to visualize and measure these changes accurately. Their study results found that changes in the smallest blood vessels might limit the oxygen supply to the brain -a phenomenon referred to as capillary dysfunction.
Their initial studies suggest that capillary function was severely disturbed both in aged and Alzheimer's-like mice. As a result, Dr. Jimenez and his team propose to test potential therapies targeting this mechanism to slow the progression of Alzheimer's.
Research Plan
Dr. Jimenez and colleagues will conduct further studies with Alzheimer's-like mice to expand on their earlier findings. The researchers will measure the brain's access to oxygen in these models using novel optical scanning methods that Dr. Jimenez pioneered as a graduate student. The scientists will examine if brain images and blood/brain fluid protein levels in these mice are comparable to those reported in humans. Finally, the researchers will test to see if an FDA approved drug is able to improve capillary dysfunction in these models and enhance oxygen delivery to the brain.
Impact
The results of this effort will shed new light on the link between changes in blood flow in the brain that could be a characteristic of Alzheimer's. Understanding this pathway may also give rise to novel diagnostic and treatment avenues for further exploration.
This project is sponsored by the Alzheimer's Association, Colorado Chapter.
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