2021 Alzheimer's Association Research Fellowship (AARF)

Resilience Mechanisms Underlying Dominant Inherited Alzheimer’s Disease

How might non-genetic factors impact disease onset and progression in dominantly inherited Alzheimer’s?

Jorge Llibre Guerra, M.D., M.S.
Washington University in St.Louis
St. Louis, MO - United States

Background

Many researchers believe that multiple factors may contribute to Alzheimer’s disease, including lifestyle, environment, and genetics, and the effect of these contributors may accumulate over time. Preventing or slowing disease progression may be more successful if interventions are implemented before extensive brain changes have occurred. 

There are deterministic genes that directly cause a disease in any individual who inherits them, referred to as familial or dominantly inherited Alzheimer’s. Among individuals with dominantly inherited Alzheimer’s, there may be differences in age at onset and disease progression, even within families that carry the same genetic variation. This suggests that non-genetic factors may play a role in modifying aspects of the disease and the time of disease onset. 

Studies have identified potential non-genetic factors that occur throughout life that may impact cognitive decline in dementia. However, little is known about how these factors contribute to age of onset or disease progression in individuals with dominantly inherited Alzheimer’s.
 

Research Plan

Dr. Jorge Llibre Guerra believes that non-genetic factors may modify the course of disease in individuals with dominantly inherited Alzheimer’s. Dr. Llibre Guerra and colleagues will use data from the Dominantly Inherited Alzheimer’s Network (DIAN), an international consortium that collects data from families with dominantly inherited Alzheimer’s. The researchers will study the influence of non-genetic factors on trajectories of neuroimaging, biomarker, clinical, and cognitive measures over time to look at these potential associations. 

Dr. Llibre Guerra and research team will examine the extent to which life-course factors (such as level of education) and health factors (such as diet and physical activity) may influence the age of onset and rate of cognitive decline in individuals with dominantly inherited Alzheimer’s. In addition, the researchers will study the impact of these non-genetic factors on the biological brain changes associated with Alzheimer’s.
 

Impact

The results may shed light on the impact of non-genetic factors on disease trajectory in dominantly inherited Alzheimer’s and these learnings may be relevant for late onset Alzheimer’s as well. The findings may identify risk factors that are modifiable and suggest the best time for an intervention.