2022 Alzheimer's Association Research Fellowship (AARF)

The role of epilepsy in Tau propagation in Alzheimer's Disease

How can brain seizures promote the clumping of dementia-related tau protein in the brain?

Aaron Barbour, Ph.D.
University of Pennsylvania
Philadelphia, PA - United States

Background

Nerve cells in the brain use electrical signals to communicate with one another. Such communication is essential for many cognitive functions, including learning and memory. In individuals with epilepsy, however, these electrical signals become overactive, a phenomenon known as “hyperexcitability”, and lead to seizures. Hyperexcitability is also a feature of Alzheimer’s, and it may be linked to a higher risk of seizures in individuals with Alzheimer’s. Yet, the biological mechanisms underlying this link remain unclear.

In recent studies with nerve cells grown in a laboratory dish, scientists found that hyperexcitability can lead to the production of dementia-related tau protein. This finding suggests that seizures, including epileptic seizures, can promote the spread of tau and the development of Alzheimer’s.

Research Plan

Dr. Aaron Barbour and colleagues will study how seizures promote tau accumulation in mice genetically engineered to develop Alzheimer’s-like brain changes and in human brains. First, they will inject Alzheimer’s-like mice with tau and induce seizures in the mice. They will then use scans to measure the spread of this tau in the mice brains, especially in brain regions vulnerable to dementia. Next, the researchers will compare brain scans to observe tau build-up (clumping) in the brains of individuals who had either Alzheimer’s with seizures or Alzheimer’s without seizures. This comparison will assess whether tau clumping may have differed due to seizures. Lastly, Dr. Barbour’s team will examine mouse brains to determine how abnormal activity in specific brain cells may promote tau spreading, and whether this accumulation may occur very early in the progression of Alzheimer’s – before the creation of beta-amyloid protein (one of the hallmarks of Alzheimer’s) and other disease-related factors.    

Impact

Results from Dr. Barbour’s study could refine our understanding of how abnormal brain cell activity and disease-related tau production are linked. They could also lead to novel methods of detecting dementia at an early stage.