New Grant Will Examine Link Between ‘Dirty’ Brains and Alzheimer’s

A new $3.2 million grant will bring together biomedical scientists and mechanical engineers in an effort to develop a detailed understanding of the brain’s waste removal system.  The research could have significant implications for diseases like Alzheimer’s that arise when this system breaks down and toxic proteins accumulate in the brain.

The new research is being funded by the National Institute on Aging and will study the glymphatic system.  This system is unique to the brain and was first described by Maiken Nedergaard, M.D., D.M.Sc., the co-director of the University of Rochester Center for Translational Neuromedicine, and her colleagues in 2012, who showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste.  Subsequent research has shown that the glymphatic system is more active while we sleep and can be damaged by stroke and trauma. 

The new grant will support a research collaboration between Nedergaard’s lab and John Thomas, Ph.D., Douglas Kelley, Ph.D., and Jessica Shang, Ph.D., with the University of Rochester’s Department of Mechanical Engineering.  

Thomas, Kelley, and Shang are experts in the field of fluid dynamics.  While this discipline is traditionally associated with the study of ocean currents, weather patterns, plate tectonics, electromagnetic fields, and industrial systems that employ fluids or gases, the principals of fluid dynamics are also increasingly being applied to study biological processes such as blood flow and now the glymphatic system.

The Rochester team is also partnering with Ali Ertürk, Ph.D., with the Institute for Stroke and Dementia Research at Ludwig Maximilians University of Munich.  Ertürk and colleagues has developed a method that alters the chemistry of biological tissue, a process which essentially renders mice transparent and will enable researchers to peer more deeply into the brain to observe the glymphatic system in action.  Ertürk also holds an adjunct faculty position in Center for Translational Neuromedicine at the University of Rochester.

The new animal model, combined with advanced methods to observe, track, and model how CSF flows and carries waste out of the brain, should provide scientists with a more detailed blueprint of the structure and function of the glymphatic system. 

This, in turn, will help researchers identify factors – such as age, injury, sleep deprivation, or genetic flaws – that can prevent the glymphatic system from doing its job.  While the study will specifically look at how the brain removes tau and amyloid beta, two proteins associated with Alzheimer’s disease, the findings could have relevance for a range of neurological disorders or point to a new ways to deliver drugs to the brain.