2024 Alzheimer's Association Research Grant (AARG)
Tau and cortical functional network dynamics in Alzheimer's disease
How are communication networks in the brain impacted by the distribution of tau tangles?
Yuta Katsumi, Ph.D.
Harvard University
Boston, MA - United States
Background
Tau is a protein that helps maintain the structure of brain cells. In Alzheimer’s and other brain diseases, the shape of tau protein becomes modified or “misfolded,” a change that may contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage. Brain diseases believed to result from the abnormal modification of tau are called “tauopathies”.
Emerging evidence suggests that the distribution of tau tangles in the brain can lead to different symptoms of dementia. These tangles may be spread through brain regions that communicate with each other via nerve cell networks (circuits) that connect the regions. These networks, which help control memory and other cognitive functions, have a complex structure that includes hub-like points called “nodes,” which connect smaller areas within the brain.
Disruption to these networks in Alzheimer's is characterized by the progressive breakdown of neural connections, leading to impaired communication between brain regions. More research is needed to better understand how tau tangle distribution relates to brain network dysfunction and how this can impact the presentation of memory impairment in Alzheimer’s.
Research Plan
Dr. Yuta Katsumi and colleagues will enroll 30 individuals with late-onset Alzheimer’s Disease (LOAD) from the Massachusetts Alzheimer’s Disease Research Center and 30 people with early-onset Alzheimer’s Disease (EOAD) from The Longitudinal Early-onset AD Study (LEADS) at Indiana University. The research team will utilize different types of brain scans to evaluate Alzheimer’s-related brain changes and correlate their observations with cognitive impairment in participants. In addition to evaluating brain structure for the presence of beta-amyloid plaques and tau tangles, the two hallmark brain changes observed in Alzheimer's, the team will use another type of brain scan, called functional magnetic resonance imaging (MRI) to assess brain region activity during memory tasks. The researchers will use these data to assess how the buildup of tau tangles in the brain, problems with brain communication, and memory loss are connected.
Impact
If successful, the results of this study may provide a deeper understanding of the underlying mechanisms of Alzheimer’s and the diverse ways it can manifest. These findings may also lead to new research tools for early detection and diagnosis of Alzheimer’s.