2021 Alzheimer's Association Research Fellowship (AARF)

Relating Longitudinal Structural Changes to AD Biomarkers and Cognition

What may be early brain structure changes associated with developing Alzheimer’s?

Tammy Tran, Ph.D.
Stanford University
Redwood City, CA - United States

Background

Research suggests that brain changes observed in Alzheimer’s disease start decades before clinical signs, including decline in memory, are evident.

One of the brain changes associated with Alzheimer’s is the accumulation of an abnormal form of the tau protein into tangles. More than 20 other brain diseases also have changes in the tau protein. In disease, tau undergoes a number of specific changes that make it sticky, and it then clumps together to form the tangles. These tangles may negatively affect brain cell function and could contribute to cell death. 

Dr. Tammy Tran believes that tau accumulation may also drive early structural changes in the brain. Preliminary research from her group suggests that increased tau accumulation is associated with thinning and loss of volume in the medial temporal lobe, a brain region that is important for learning and memory; this region also changes early in Alzheimer’s. However, it is not known if these early changes in brain structure, or other biomarkers, predict if an individual will develop Alzheimer’s.

Research Plan

Dr. Tran and colleagues will study the relationship between tau accumulation and early structural changes in areas of the brain critical for learning and memory. The researchers will draw on an existing cohort of 200 cognitively unimpaired older adults from the Stanford Aging and Memory Study and will follow a subset of about 50 individuals from this study for four years. Using high-resolution brain imaging techniques (magnetic resonance imaging or MRI), Dr. Tran and team will investigate how tau accumulation is associated with the thickness and volume of the medial temporal cortex and connected brain structures. They will investigate these brain changes and relate them to cognitive function in cognitively unimpaired older adults at the first visit and over the four-years of follow-up. 

In addition, the researchers will use advanced statistical methods and a new machine-learning framework to study how tau accumulation and brain structure changes over time may predict future cognitive decline.

Impact

The results may contribute to the understanding of early disease-related brain changes, and how structural changes in specific brain regions relate to other changes in the earliest stages of Alzheimer’s and other brain diseases. If successful, the findings may help identify the earliest potential brain changes indicative of Alzheimer’s.