Paula Grammas, executive director of the George & Anne Ryan Institute for Neuroscience at the University of Rhode Island and a Thomas M. Ryan professor of neuroscience, was recently elected to the American Association for the Advancement of Science Circle of Fellows in recognition of her pioneering research into the role of blood vessels in Alzheimer’s disease.
Grammas is best known for her research into the role blood vessels and inflammation play in the development of neurodegenerative diseases. She has been the principal investigator or co-investigator on more than $26 million in research grants from the National Institutes of Health, the Alzheimer’s Association, the American Foundation for AIDS Research and other agencies and foundations. Grammas recently spoke with Providence Business News about her work.
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PBN: You’ve been studying the connection between vascular health and Alzheimer’s disease since before the link was well-established in the medical community. What developments or discoveries turned general wisdom in that direction?
GRAMMAS: A lot of work until now has focused on a particular hypothesis that has yet to pay off, so there’s more willingness today to look at other ideas. Meanwhile, there is growing evidence that cardiovascular risk factors such as high blood pressure and high cholesterol increase your risk for developing Alzheimer’s and other dementias. That has helped expose the field to thinking about blood vessels, which is a path our lab was pursuing at a time when there weren’t a lot of people looking into this aspect of the disease.
There is also increased acceptance of the fact that Alzheimer’s is likely not a single disease but a group of diseases. This too has helped generate more interest in looking to the multiple factors that could be playing an early role in the development of Alzheimer’s.
However, in general, the role of blood vessels in the disease, as well as how inflammation and the immune system may also play a role in its development, remain vastly under-explored areas. When our institute was formed a few years ago, we made it a focus to recruit other scientists who have been pursuing these under-explored paths toward the treatment and prevention of neurodegenerative diseases.
PBN: Could you describe the connection between vascular health and Alzheimer’s disease?
GRAMMAS: In Alzheimer’s, we see that the blood-brain barrier gets leaky, and the cells in the blood vessel walls become over-activated or disturbed. Instead of making proteins that support brain function, they produce inflammatory proteins and neurotoxins that are damaging to the brain cells. It starts a vicious cycle where these inflammatory proteins and neurotoxins will in turn damage the blood vessels, leading the blood vessels to produce more inflammatory proteins and neurotoxins.
A number of factors may cause this over-activation to happen, such as high cholesterol, high blood pressure, or high blood sugar. This is an area we are actively exploring.
PBN: Where is your current research looking in this field?
GRAMMAS: We are currently progressing on two different, complementary paths. Our basic science laboratory is continuing to explore how blood vessels may be playing a role in the death of brain cells – particularly how cardiovascular risk factors such as hypertension and diabetes could be contributing to the over-activation process in Alzheimer’s.
Our second focus is to translate our basic science work into clinical trials. We will shortly be testing the idea that inhibiting this over-activation process could help stop or slow some of the brain changes we see in this disease.
PBN: What other neurodegenerative diseases are linked to vascular conditions?
GRAMMAS: There are diseases where we know blood vessels are involved [such as] stroke and vascular dementia. Then there are diseases where we strongly suspect there is a vascular component [such as] Parkinson’s and ALS, but it hasn’t been examined and should be. Again, our institute is focused on pursuing some of these under-explored paths.
PBN: Where do you think the field of Alzheimer’s disease research will be in 10 years?
GRAMMAS: I think we will see wide acceptance of the fact that it is a multifactorial disease. This change in the way we think about Alzheimer’s will help us to develop a more sophisticated approach to therapy – as with HIV, it is likely patients will receive a cocktail of therapeutic interventions versus one magic bullet.
Also, we know that nearly 40 percent of dementias are preventable and that lifestyle choices, especially in midlife, impact the development of late-life dementias, including Alzheimer’s. I am hopeful that 10 years from now, people will know they can take a proactive role in preventing or slowing neurodegenerative disease.
Rob Borkowski is a PBN staff writer. Email him at Borkowski@PBN.com.
