Investigating neutrophilic inflammation as an APOE genotype-specific mediator of neuroinflammation and cognitive decline in aging

This research program investigates the role of neutrophilic inflammation as an APOE genotype-specific mediator of neuroinflammation and cognitive decline during aging. The Hensley-McBain laboratory focuses on defining inflammatory drivers of end-organ damage in chronic age-related diseases with the explicit aim of discovering therapeutic targets to prevent or slow neurodegeneration and related cardiometabolic decline. The lab’s work integrates animal models and in vitro systems to connect microbial dysbiosis, innate immune responses, and genotype-specific susceptibility to brain inflammation and cognitive impairment. A central premise of the work is that neutrophils—innate immune cells traditionally studied in peripheral inflammation—may act differently depending on APOE genotype, thereby shaping neuroinflammatory cascades and outcomes in aging brains.

By identifying how neutrophil behavior, trafficking, and inflammatory mediator production vary with APOE alleles, the research seeks to reveal mechanisms by which genetic risk factors interact with immune responses to precipitate cognitive decline. The laboratory’s objectives reflect a translational and capacity-building mission. Scientifically, the group aims to develop new therapies and diagnostics for Alzheimer’s disease and other age-related conditions by deepening understanding of how inflammation and aging intersect. Methodologically, the program leverages mouse models that recapitulate APOE genotype variation and age-related immune changes, coupled with in vitro assays to dissect cellular and molecular pathways.

Beyond bench research, Hensley-McBain’s program emphasizes expanding clinical research capacity and workforce development in Montana. The lab seeks to bring Alzheimer’s disease and neurodegeneration clinical trials to the state through expansion of the Montana Center for Aging Research and Education, thereby increasing community access to novel interventions and diversifying participant populations.

Collectively, this research integrates immunology, aging biology and genetics to target a pressing public health problem—age-related cognitive decline—through both mechanistic discovery and translational pathways. By testing the hypothesis that neutrophilic inflammation operates as an APOE genotype-specific mediator of neuroinflammation and cognitive deterioration, the lab hopes to identify actionable biomarkers and targets for therapeutic modulation. The program’s combined focus on rigorous preclinical science, clinical trial infrastructure development, and training positions it to advance understanding of genotype-immune interactions in aging and to foster regional capacity for Alzheimer’s research and care.