2023 Alzheimer's Association Clinician Scientist Fellowship (AACSF)
Individualized Prediction of Tau Propagation Using Diffusion Tensor Imaging
How does the spread of disease-related tau protein differ in different individuals at risk for Alzheimer’s?
Christopher Brown, Ph.D.
University of Pennsylvania, Perelman School of Medicine
Philadelphia, PA - United States
Background
The brain cell’s nutrient and energy transport system is organized in parallel strands like railroad tracks. These tracks allow nutrients to travel across the cell, delivering key materials to the cells, providing them with energy and keeping them healthy. A protein called tau helps keep these tracks straight. In Alzheimer’s and other brain diseases, however, tau’s shape becomes modified, or “misfolded”, a change that may contribute to tau accumulations called tangles. Tau tangles are a hallmark of Alzheimer’s, and they may be involved in subsequent nerve cell damage.
Researchers are now examining the mechanisms that may underlie how disease-related tau spreads through the brain. According to recent studies, brain regions with tau tangles relate to changes in network connectivity, or the ability of multiple brain regions to communicate with one another. These changes, in turn, may be associated with damage to white matter (the primary wiring system in the brain). White matter is used by nerve cells to communicate with one another by sending signals quickly, a process that also involves synapses (specialized structures in between nerve cells). However, researchers do not yet understand the exact links between white matter damage, network connectivity changes and tau spreading in Alzheimer’s.
Research Plan
Dr. Christopher Brown and colleagues will devote their research grant to clarifying these links. For their effort, they will analyze positron emission tomography (PET) and diffusion magnetic resonance imaging (dMRI) brain scan data from participants in two large studies of aging. First, the researchers will look for specific places in the brain where tau accumulates (places called tau “epicenters”), and determine how these epicenters may be related to patterns of connectivity changes across different brain regions. Second, they will examine areas of white matter linked to tau epicenters, and look for subtle structural damage that may promote tau accumulation in these areas. The researchers expect that different individuals will develop tau epicenters differently.
Impact
Results from Dr. Brown’s study could help clarify how and where tau accumulation takes place in Alzheimer’s and other brain diseases. They could also promote the development of individualized disease therapies that target disease-related tau.
Funding support for this project has been made possible by the Fred A. and Barbara M. Erb Family Foundation. This awardee is recognized as a Fred A. Erb Clinical Research Science Fellow for the Alzheimer's Association.