Defining the contributions of tau pathology in the amygdala to increasing depressive symptoms in aging

BACKGROUND Amygdala tau accumulates in cognitively normal individuals and may contribute to neuropsychiatric changes. METHODS Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we investigated relationships among cross‐sectional and longitudinal tau ([18F]Flortaucipir [FTP] positron emission tomography), changes in depressive symptoms and memory, and amyloid beta and apolipoprotein E ( APOE) ε4 status. We report secondary analyses from the Berkeley Aging Cohort Study (BACS). RESULTS Longitudinal increases in depressive symptoms were associated with higher baseline FTP and increasing FTP in the amygdala. Relationships between FTP and depressive symptoms were strongest in APOE ε4 carriers, with moderation effects replicating in BACS. Entorhinal FTP did not show associations with depressive symptoms beyond variance explained by the amygdala but showed some specific associations with memory decline. DISCUSSION Our findings indicate the strongest coupling between tau accumulation and depressive symptoms in APOE ε4 carriers and reinforce the importance of amygdala tau in understanding neuropsychiatric changes in older adults. Highlights There is a lack of research focused on the role of tau in the amygdala in cognitively normal older adults. Amygdala tau is related to both worsening depressive symptoms and declining memory performance. APOE ε4 carriers seem to drive positive tau‐depressive symptom associations. Focusing on the amygdala tau is useful for understanding neuropsychiatric trajectories in cognitively unimpaired older adults.