Medial amygdalar tau is associated with mood symptoms in preclinical Alzheimer's disease.

Background: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms.

Methods: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In the tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores.

Results: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala, and tau binding in these regions was associated with mood symptoms. Across amygdalar divisions, amyloid-positive individuals had relatively higher regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex, but medial amygdala to retrosplenial cortex was lower. Medial amygdala to retrosplenial connectivity was negatively associated with anxiety symptoms, as was retrosplenial tau.

Conclusions: Our findings suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may relate to early mood symptoms in AD.