2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Identifying Astrocyte-Mediated Vasomotion Underlying AD Pathogenesis

What role do the brain’s support cells play in removing waste from the brain?

Xiaoqing Alice Zhou, Ph.D.
Massachusetts General Hospital
Boston, MA - United States

Background

Alzheimer’s is associated with hallmark brain changes including the accumulation of the proteins beta-amyloid and tau into abnormal plaques and tangles, respectively. While scientists do not know exactly why the accumulation of beta-amyloid and tau occurs, one factor may be through impairments in the brain’s waste removal system, known as the glymphatic system.

In cognitively unimpaired individuals, the glymphatic system successfully removes waste products produced by nerve cells from the brain. Brain blood vessels (tube-like structures), including small vessels called arterioles, play an important role in transporting waste out of the brain. Healthy arterioles constantly dilate and contract.  This process, called vasomotion, may help “guide” waste out of the brain. Support cells in the brain known as astrocytes have been shown to regulate arteriole vasomotion and drive waste clearance. 

Studies have shown that glymphatic dysfunction may be an indication of brain aging and brain cell death. However, it is not clear how astrocytes mediate changes in vasomotion that lead to glymphatic dysfunction in Alzheimer’s.

Research Plan

Dr. Xiaoqing Zhou and colleagues will study glymphatic dysfunction and waste clearance in the brains of genetically engineered Alzheimer’s-like mice. The researchers will use state-of-the-art, noninvasive brain scanning techniques (multimodal functional magnetic resonance imaging, fMRI) to detect tiny changes in vasomotion and waste clearance in brain arterioles of the mice. The team will conduct experiments on the mice to track changes in vasomotion and waste clearance over time in two brain areas impacted in Alzheimer’s (the cortex and the hippocampus). Dr. Zhou and colleagues will also study astrocyte activity underlying glymphatic dysfunction in the mice.

Impact

The findings may help clarify the role of the glymphatic system in Alzheimer’s and have the potential to identify new targets for therapies aimed at slowing the progression of the disease.