University of Oregon scientist Ashley Walker focuses on what happens as arteries stiffen with age, research that has led to possible connections to Alzheimer’s disease.
Walker, who joined the Department of Human Physiology in 2017, is expanding that line of thinking as part of her overall research program in the Aging and Vascular Physiology Laboratory, which she leads.
“In the past, Alzheimer’s disease was considered to be just a disease of the neurons in the brain,” Walker said. “The scientific community is now realizing that other cells in the brain are likely contributors.”
That idea took root in 2013 when scientists at the Wake Forest School of Medicine and University of Pittsburgh reported in the journal Neurology that Alzheimer’s patients with increased arterial stiffness were up to four times more likely have the disease’s tell-tale signs of visible plaque on their brain scans.
In humans, she said, large arteries begin stiffening around age 50, while late-onset Alzheimer’s disease is usually diagnosed at age 75. That means, she said, that small blood vessels in the brain are exposed to these damaging effects for a long period of time, eventually leading to less blood flow to the brain and leaky blood vessels.
“Arteries and capillaries are instrumental to brain function as they deliver oxygen and nutrients,” Walker said. “Without a proper control of blood flow, neurons are not able to function and this could lead to the problems with memory that are seen in patients with the disease.”
In her previous research, Walker has identified cellular changes that have affected how arteries function in old age, resulting in high blood pressure or atherosclerosis.
Last September Walker received a one-year, $424,000 grant from the Institute on Aging at the National Institutes of Health to dig deeper at the role of arterial stiffness on cognitive impairment and other brain diseases. She was also previously awarded a NIH career development award to explore mechanisms for cerebral artery dysfunction with aging.
This spring, the NIH awarded her a $2.1 million grant over five years to launch a project that will look at large artery stiffness in mice that are predisposed to producing amyloid plaques, a key feature of Alzheimer’s disease. The project, she said, will explore what for now is only a correlation between large artery stiffness and dementia.
“Two of the biggest risk factors for Alzheimer’s disease are old age and cardiovascular disease, but we do not understand why these are risk factors,” Walker said. “As we get older, our arteries become stiffer. This increase in stiffness occurs mostly in the large arteries, such as the aorta and carotid arteries.”
Her work also has caught the attention of the Alzheimer's Association, which recently awarded her a three-year $150,000 grant. Although laboratory research is delayed because of the coronavirus crisis, preparation is underway.
She’s also involved in a collaboration with Dr. Nabil Alkayed at Oregon Health and Science University in Portland, a project designed to explore the relationship between estrogen deficiency, vascular dysfunction and dementia. While women are two times more likely to develop Alzheimer’s disease, she said, the project aims to identify potential new interventions for both men and women.
This project has been boosted by a grant from the John L. Luvaas Family Fund of the Oregon Community Foundation. In addition to supporting the research, it also will assist lab members at every stage of their training and careers, and introduce UO students to mentorship and equipment through their access to opportunities at OHSU.
Walker began her UO research program with a career development award from the NIH and with funds donated by taxpayers through the Oregon Tax Checkoff for Alzheimer’s Research Fund, which is administered by OHSU’s Layton Aging and Alzheimer’s Disease Center.
“If we identify the mechanisms of these age-related changes, we may be able to develop new therapies to treat or prevent Alzheimer’s disease,” Walker said.
—By Jim Barlow, University Communications