Dr. Stevens’ project examines how viral infections outside the brain influence brain immunity and contribute to AD. While amyloid accumulation is a hallmark of AD, systemic infections such as influenza may modify disease progression by disrupting immune balance.
Her lab previously demonstrated that brain-resident immune cells, including microglia and border-associated macrophages (BAMs), play an important role in clearing amyloid beta. However, aging and peripheral immune challenges can impair this protective function. Building on this work, the Stevens team hypothesizes that influenza infection is first sensed at the brain’s borders by BAMs and related immune cells, which then transmit signals inward that alter microglial activity, inflammatory signaling, and amyloid clearance.
To test this, the team will determine how influenza infection reshapes immune cell populations within the brain and assess its impact on plaque accumulation in AD mouse models. They will define how T cell-derived cytokines influence the BAM phenotype and function, including their ability to clear amyloid beta and tau, using both human stem cell-derived systems and in vivo assays. In addition, they will develop and validate models of vascular amyloid deposition to determine how peripheral infection differentially affects amyloid buildup in blood vessels versus brain tissue.
Through collaborations with other laboratories of the Neuroimmune Consortium, the Stevens team will integrate findings on astrocyte signaling, genetic risk modifiers, and monocyte-derived macrophages to develop a comprehensive understanding of how systemic viral infection influences Alzheimer’s progression and identify potential cellular and molecular intervention points.
