2022 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Linking Neuronal Hyperexcitability with Amyloid and Tau Pathology in AD

How does brain seizure activity impact biological brain changes associated with Alzheimer’s and progression of the disease?

Alice Lam, M.D.
Massachusetts General Hospital
Boston, MA - United States

Background

Nerve cells in the brain use electrical signals to communicate with one another. This communication is essential for brain function, including learning and memory. In individuals with Alzheimer’s, however, these electrical signals can become overactive, a phenomenon known as “hyperexcitability.” Research suggests that this excessive nerve cell activity may contribute to a higher risk of seizures in individuals with Alzheimer’s. As many as 20 percent of people who have Alzheimer’s experience brain seizures, which resemble those experienced by people who have epilepsy. Individuals who have Alzheimer’s with seizures tend to experience more rapid declines in brain function than those who have Alzheimer’s without seizures. However, this sub-population of individuals who have Alzheimer’s with seizures is not well studied.

Research Plan

Dr. Alice Lam and colleagues believe that seizures and other forms of nerve cell hyperexcitability may arise early in the progression of Alzheimer’s and accelerate biological brain changes associated with cognitive decline. The researchers will recruit eight individuals who have Alzheimer’s with seizures to undergo multiple assessments at a baseline time point as well as follow-up assessments after 18 months. Participants will undergo at-home, overnight scalp electroencephalogram (EEG) recordings to measure brain activity, including hyperexcitability. In addition, the research team will administer cognitive tests and brain scans (magnetic resonance imaging, MRI, and positron emission tomography, PET), which measure the accumulation of amyloid-beta plaques and tau tangles, two hallmark brain changes associated with Alzheimer’s. Dr. Lam and colleagues will study the relationships between the amount of hyperexcitability, cognitive functioning, and the extent and location of amyloid-beta plaques and tau tangles in the brain.

Impact

If successful, the results of this project may advance our understanding of the role of nerve cell hyperexcitability in Alzheimer’s. Focusing on detecting and reducing hyperexcitability may lead to novel treatment targets to delay the progression of Alzheimer’s.