Center for Healthy Minds

Chronic inflammatory diseases can compromise brain health and increase dementia risk, but why and how that happens is a lingering scientific puzzle.

A multi-disciplinary team of University of Wisconsin–Madison researchers is set to launch a five-year investigation into this question.

With the support of a $3.8 million grant from the National Institutes of Health, the team plans to use a combination of brain imaging, blood-based biomarkers and animal models of Alzheimer’s disease and asthma to establish how, for whom and under what circumstances chronic systemic inflammation may contribute to or accelerate Alzheimer’s Disease and related dementia.

The aim is to identify links between systemic inflammation and neuroinflammation by measuring changes in brain immune cells associated with airway inflammation. Asthma is an inflammatory lung disease affecting nearly 26 million Americans. Since asthma usually comes on early in life, it provides an extended window for medical intervention. That makes it an attractive target for evaluating how systemic inflammation may impact brain health and confer a greater risk for Alzheimer’s disease.

Melissa Rosenkranz

“Since asthma is a disease that typically begins in the first decade of life, if it’s true that asthma contributes to the cascade of events that contribute to the pathology of Alzheimer’s disease, we would have a much longer window to intervene to protect the brain than any other risk factor that we’re currently aware of,” says Melissa Rosenkranz, a UW–Madison psychiatry professor and distinguished chair of contemplative neuroscience at the Center for Healthy Minds. Rosenkranz is leading the study along with Dr. Nizar Jarjour, a professor in the Department of Medicine at the Wisconsin School of Medicine and Public Health.

“This study will also provide insight into how we can potentially intervene,” Rosenkranz says.

The team will examine patterns of brain-derived biomarkers and their relation to asthma severity, in addition to the extent to which asthma accelerates accumulation of Alzheimer’s disease pathology. The researchers will also assess the relationship between neuroinflammation and cognitive performance.

One critical goal of this study is to identify which “signaling pathways” — molecular messengers mobilized during an asthma response — lead to activation of brain immune responses and potentially contribute to the increase in Alzheimer’s risk. The ultimate goal is to spur development of novel treatments that precisely target these pathways. Zeroing in on these pathways could identify specific intervention targets, enabling precision medicine approaches to delay onset, slow progression and potentially prevent neurocognitive illness.

This research could also address important health disparities, due to a disproportionately high prevalence of asthma among racial minorities and low-income communities. Similar disparities exist for Alzheimer’s disease, and this study could help identify opportunities to address them.

This work emerged from a long-standing collaboration between the UW–Madison Center for Healthy Minds and physicians specializing in asthma, allergies and pulmonary medicine at the Wisconsin School of Medicine and Public Health.

Long-term, the team hopes to contribute to the prevention, reduction or delay in onset of Alzheimer’s in those with chronic inflammation. If successful, the approach could serve as a model to explore similar relationships and potential interventions in other inflammatory conditions that compromise brain health.

Alzheimer’s disease, a slow-moving degenerative brain disorder affecting memory, is the most common form of age-related dementia. Millions of Americans 65 and older live with Alzheimer’s, and few interventions are currently available to delay or prevent its progression, even though most cases are associated with a prolonged onset period.

By Heather Harris

Photo credit: ipopba