2022 Alzheimer's Association Research Fellowship (AARF)

Amygdala Tau Pathology in Preclinical Familial Alzheimer's Disease

What biological changes may happen in Alzheimer’s before memory changes in the brain structure known as the amygdala?

Stephanie Langella, Ph.D.
Massachusetts General Hospital
Boston, MA - United States

Background

In Alzheimer’s, the proteins beta-amyloid and tau accumulate to form plaques and tangles respectively, two hallmark brain changes observed in the disease. Recent studies suggest that these brain changes associated with Alzheimer’s appear decades before the clinical symptoms, including changes in memory. 

In early Alzheimer’s, tau tangles are often observed in a brain structure called the amygdala. The amygdala is an area of the brain critical for memory function as well as emotional processing and regulation. Changes in the amygdala may underlie some of the non-cognitive (or neuropsychiatric) behaviors of individuals with Alzheimer’s experience, such as depression, agitation, and apathy. However, the impact of abnormal tau tangles in the amygdala on cognitive deficits and neuropsychiatric symptoms in early Alzheimer’s is not well studied.

Research Plan

Dr. Stephanie Langella and colleagues will study abnormal tau in the amygdala, along with cognitive and neuropsychiatric symptoms associated with abnormal tau changes, in a group of individuals with the relatively rare dominantly inherited Alzheimer’s. These individuals have a mutation in a specific gene that results in the development of a form of early-onset Alzheimer’s, usually beginning in one’s forties. The researchers will recruit participants from the Colombia-Boston Longitudinal Biomarker study, which includes a large extended family in Colombia which has a high prevalence of familial Alzheimer’s. Participants will undergo neuropsychological testing and brain scans.

Dr. Langella and team will compare tau accumulation in the amygdala in individuals who have the mutation versus those who do not.  They will also study how abnormal tau in the amygdala changes over time and relates to other biomarkers of Alzheimer’s (abnormal accumulation of beta-amyloid plaques in the brain). In addition, the researchers will study the relationship between amygdala tau and cognitive and neuropsychiatric functioning.

Impact

This project may shed light on the role of abnormal tau accumulation in the amygdala and its relation to the symptoms a person may experience. The results may inform future studies of early detection and intervention in dominantly inherited Alzheimer’s and other dementias.