2023 Alzheimer's Association Clinical Scientist Fellowship to Promote Diversity (AACSF-D)
Tau Pathology in the Amygdala: Studying Neuropsychiatric Symptoms in AD
How can abnormal tau protein in a brain region linked to memory and emotion lead to depression and other psychiatric symptoms in dementia?
Jonathan Vogelgsang, Ph.D.
McLean Hospital
Belmont, MA - United States
Background
Individuals with Alzheimer’s often experience neuropsychiatric behaviors, such as agitation, depression and apathy. According to research, these behaviors may occur early in Alzheimer’s, and they may accelerate memory loss and other forms of cognitive decline in the disease. However, relatively little is known about the biological mechanisms that link neuropsychiatric disorders and dementia-related cognitive loss.
Studies have found that neuropsychiatric behaviors may result, in part, from changes in the amygdala – a brain region critical for memory function as well as emotional processing and regulation. On such change involves the protein tau. Tau molecules become misshapen (or “misfolded”) in Alzheimer’s, a process that leads to the accumulation of abnormal tau into clumps called tangles. The amygdala develops tau tangles early in Alzheimer’s, but the precise impact of these tangles in the disease is not well understood.
Research Plan
Dr. Jonathan Vogelgsang and colleagues will study how tau-related changes in the amygdala are linked to dementia-related changes in cognition and behavior. They will examine amygdala and other brain tissue from individuals who had Alzheimer’s with or without neuropsychiatric symptoms (depression or anxiety). They will also examine the individuals’ electronic medical records.
The researchers will assess whether individuals with Alzheimer’s and neuropsychiatric symptoms were more likely to have tau clumping in the amygdala than were individuals who had Alzheimer’s without these symptoms. They will then examine whether specific brain cell types in the amygdala are more vulnerable to tau tangles and beta-amyloid plaques (another brain change in Alzheimer’s); and whether specific types of tau misfolding in the amygdala may promote dementia-related depression and anxiety.
Impact
The results of this study could shed new light on the role of tau and the amygdala in Alzheimer’s-related psychiatric behaviors. They could also lead to novel dementia treatments that target tau in the early stages of disease.