2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Glymphatic Activity and Preclinical Alzheimer's Disease Pathogenesis

How is the brain’s waste removal system linked to the hallmark brain changes observed in Alzheimer’s?

Gawon Cho, Ph.D.
Yale University
New Haven, CT - United States

Background

Two of the hallmark brain changes observed in Alzheimer’s are the abnormal build of the proteins beta-amyloid and tau into amyloid plaques and tau tangles, respectively. While researchers do not know the exact reasons why these specific proteins accumulate in the brain in Alzheimer’s, one factor that may play a crucial role is the brain’s waste removal system, known as the glymphatic system. Normally, the glymphatic system successfully removes waste products produced by nerve cells from the brain. However, studies have shown that this process is impaired in Alzheimer’s. 

For their project, Dr. Gawon Cho and colleagues will study how the glymphatic system activity changes during the clinical progression of Alzheimer’s and how these changes are associated with the hallmark brain changes that are observed in Alzheimer’s.

Research Plan

Dr. Cho and the team will measure glymphatic system activity and waste removal in individuals with Alzheimer’s using state-of-the-art, noninvasive brain scanning techniques (multimodal functional magnetic resonance imaging, fMRI). For the same individuals, they will also use an imaging technique called positron emission tomography (or PET), which uses special “tracers” that measure the amount and identify the location of amyloid plaques and tau tangles in the brain. The researchers will use multiple brain scans collected for each individual over the course of two years, as well as cognitive assessment data, to examine the association between glymphatic system activity, amyloid plaque and tau tangle levels, and cognitive impairment over the clinical progression of Alzheimer’s.

Impact

Results of this study may help define the role of the glymphatic system in Alzheimer’s and have the potential to identify new targets for therapies aimed at slowing the hallmark brain changes that are observed in the disease.