Principal investigator Jennifer Munson, associate professor in the College of Engineering's Department of Biomedical Engineering and Mechanics, and co-investigators Michelle Theus, associate professor of molecular and cellular neurobiology in the Department of Biomedical Sciences and Pathobiology; Michelle Olsen, associate professor in the College of Science's School of Neuroscience; and Ian Kimbrough, assistant professor in the School of Neuroscience, have been awarded a four-year R01 grant from the National Institutes of Health's (NIH) National Institute on Aging (NIA) to investigate the clearance of amyloid protein in Alzheimer's disease.

TITLE
Interstitial fluid flow in Alzheimer's disease progression

FUNDING AGENCY
NIA / NIH

TOTAL AWARD
DIRECT: $1,358,020
INDIRECT: $828,392

DURATION OF AWARD
June 1, 2021 — March 31, 2025

KEY FACULTY PERSONNEL
PI/PD: Jennifer Munson
CO-I: Michelle Theus, Michelle Olsen, Ian Kimbrough

SIGNFICANCE
Alzheimer's disease is a devastating disease marked by cognitive decline. The reasons underlying this decline are still unclear, but it is known that Amyloid β (Aβ) aggregation and accumulation in the brain contributes to worsening cognitive deficits. Recently, it has been identified that major mediators of bulk fluid flow in the brain are implicated in the clearing of Amyloid β, including the glymphatic system, the meningeal lymphatics, and the blood vasculature. Decreased fluid flow via any of these routes can worsen accumulation of Aβ and cognitive deficits in murine models of the disease. Bulk pathways are important for understanding overall clearance from the brain; however, it does not give us insight into the underlying cellular or tissue-level mechanisms. At the cellular level, the fluid flow that cells sense is called interstitial fluid flow, and its role in Alzheimer's is, as yet, unstudied. Here we will measure, manipulate, and model interstitial fluid flow as it relates to increases in Alzheimer's pathology and alleviation of associated symptoms.