You wouldn’t think twice if someone told you that eating healthy, getting enough sleep and reducing your stress levels could significantly reduce your risk of a heart attack. But could implementing these healthy lifestyle factors help to decrease your risk of developing Alzheimer’s disease as well?

That’s the compelling question Massachusetts General Hospital researchers Filip Swirski, PhD, and Matthias Nahrendorf, MD, PhD, are beginning to explore with support from the CURE Alzheimer’s Fund.

Swirski, a Patricia and Scott Eston MGH Research Scholar, and Nahrendorf, a Weissman Family MGH Research Scholar, have been studying the role of inflammation in various diseases for the past decade, with a goal of unraveling how lifestyle factors such as stress, diet and sleep contribute to or protect from chronic inflammation and the onset of disease.

“While our major interest over the years has been to study the behavior of these cells in the context of cardiovascular disease, we have pivoted or at least added Alzheimer’s disease as one where we think these cells are important,” Swirski says.

“This is how we came to the CURE Alzheimer’s Fund,” he explains. “Rudy Tanzi, PhD—a prominent Mass General scientist who investigates Alzheimer’s disease—is also interested in inflammation, and we have been working with him using mouse models of Alzheimer’s disease to study the various inflammatory networks, specifically focusing on immune cells and how they shape, contribute to and perhaps protect against the disease.”

Inflammation: The Good, the Bad and the Puzzling

Inflammation is a response to cellular injury that is marked by a surge in blood flow to the damaged cells, blood vessel dilation, increased white blood cell activity and the release of chemical signals that help to coordinate the repair response.

The inflammatory process is essential to human health—without it we would not be able to heal a cut or recover from an illness.

While inflammation may be good for short-term healing, researchers have found that a chronic state of low-grade inflammation can do more harm than good to the body by disrupting natural biological processes and damaging healthy cells and tissues.

Chronic inflammation has been identified as a key contributor to many different diseases, including arthritis, cardiovascular disease and diabetes.

It is also known that lifestyle factors such as stress, poor sleep and a bad diet can increase inflammation levels in the body, but researchers are still working to understand how this process works on a biological and molecular level.

Inflammation and the Brain

There is even less known about how chronic inflammation affects biological processes in the brain, though researchers are starting to make progress here as well.

Matthias Nahrendorf, MD, PhD

“Compared to other organ systems we’re at humble beginnings,” Nahrendorf says. “We do understand that the brain can be influenced by immune cells and that there are resident immune cells, called microglia, that live in the brain. “

Nahrendorf and Swirski have a research project underway to study the influence of systemic inflammation on processes that occur outside of the brain and within the brain itself.

They are using a genetically engineered mouse model with mutations that cause the mice to develop an Alzheimer’s-like disease. “They get plaques, they get amyloid deposition and they experience cognitive decline,” Nahrendorf explains.

By observing how the disease process is altered in mice by the introduction of psychosocial risk factors such as stress and a lack of sleep, Nahrendorf and Swirski hope to learn more about how these factors affect disease risk in humans. They will also study how microglia interact with amyloid plaque in the brain and if these interactions help to promote or prevent the onset of disease.

It may be that strategies that help to curb the negative effects of chronic inflammation in the body or the brain could help to delay or halt the onset of Alzheimer’s disease, much in the same way that living a healthy lifestyle can reduce the risk of a heart attack.

“If there is a key word here, it is balance,” Swirski says. “Inflammation is a necessary process. But too much inflammation can be harmful, or an inflammatory response of a particular quality may be harmful. The key is to understand those processes and to harness the beneficial effects of inflammation while blocking or preventing those that are harmful.”

CURE Alzheimer’s Provides Crucial Support

The majority of Swirski and Nahrendorf’s research thus far has investigated the role of inflammation in cardiac disease or across organ systems. Expanding their work to include Alzheimer’s disease has been a journey into uncharted territory—one made possible through early support from the CURE Alzheimer’s Fund.

The Massachusetts-based nonprofit organization was established to support new approaches to Alzheimer’s disease research with the hope of accelerating the development for new treatments. Many of these ideas may be too early or unproven for traditional sources of funding such as a federal grant from the National Institutes of Health (NIH).

“CURE Alzheimer’s has been a fantastic organization”, Swirski says. “Applying for an NIH grant for Alzheimer’s disease research without having any experience would have been be an uphill battle. CURE Alzheimer’s has given us the seed money to ask questions that are relevant to Alzheimer’s, and we will use that work as a building block to apply for NIH funding down the road.”

Reprinted with permission from the Massachusetts General Research Institute Blog, January 29, 2019