The unique contribution of tau pathology in the amygdala on depressive symptoms in cognitively normal older adults

Poster Session A - Saturday, April 13, 2024, 2:30 – 4:30 pm EDT, Sheraton Hall ABC

Teodora Z. Markova¹ (teodoramarkova@brandeis.edu), Corrina Fonseca², Claire J. Ciampa¹, Alice Murphy², Susan M. Landau^2,3, Theresa M. Harrison², Anne S. Berry^4,5; ¹Department of Biology, Brandeis University, Waltham, MA, USA, ²Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA, ³Lawrence Berkeley National Laboratory, Berkeley, CA, USA, ⁴Department of Psychology, Brandeis University, Waltham, MA, USA, ⁵Volen Center for Complex Systems, Brandeis University, Waltham, MA, USA

Early tau accumulation in medial temporal lobe includes the amygdala, although many studies focus on regions such as the entorhinal cortex. Accumulation of tau in the amygdala may contribute to the notable changes in emotional regulation that often precede Alzheimer’s disease. We analyzed cognitively normal older adults (60–94 years, baseline Geriatric Depression Scale, GDS<=6) from the Alzheimer’s Disease Neuroimaging Initiative. 441 participants had at least one tau PET scan and a subset had an Aβ PET scan (n=436), APOE ε4 status (n=403), and longitudinal GDS scores (n=377). APOE ε4 carriers and Aβ positive individuals had the highest levels of amygdala tau (APOE t(400)=4.81, p<.001, Aβ t(433)=5.73, p<.001), as well as the greatest longitudinal increases in amygdala tau over time (n=178, APOE t(173)=3.64, p<.001, Aβ t(175)=3.73, p<.001). There were no direct relationships between cross-sectional or longitudinal amygdala tau and longitudinal GDS (cross-sectional r=.07, p=.139, longitudinal r=.03, p=.675). However, higher baseline amygdala tau predicted worsening GDS in APOE ε4 carriers (t(353)=2.66, p=.012) and in females (t(371)=2.22, p=.027), even when adjusting for entorhinal tau burden. Longitudinal amygdala tau also interacted with sex (t(167)=2.20, p=.029) and marginally interacted with APOE status (t(165)=1.78, p=.077) to predict longitudinal GDS, again including adjustments for entorhinal tau slopes. No interactions were found with cross-sectional (t(369)=0.27, p=.787) or longitudinal (t(167)=1.19, p=.237) amygdala tau and Aβ status. These results suggest that amygdala tau contributes to changes in depressive symptoms - particularly in those at a higher risk for developing Alzheimer’s Disease – independent of the effects of entorhinal tau.

Topic Area: EMOTION & SOCIAL: Development & aging