Tau-PET pathology in the subregions of the amygdala and its associations with cognitive performance and neuropsychiatric symptoms in autosomal dominant Alzheimer's disease.

Abstract

Background: The amygdala plays a role in behavior and emotional response and is vulnerable to Alzheimer's disease (AD) pathology, yet little is known about amygdala tau accumulation before clinical symptom onset. To investigate whether certain amygdala nuclei are particularly vulnerable to degeneration and might underlie early neuropsychiatric symptoms in AD, we aimed to characterize subregional amygdala tau pathology and its correlates associations with established biomarkers of early AD and cognitive-behavioral measures in Presenilin-1 E280A mutation carriers of autosomal dominant AD.

Methods: Participants included 25 cognitively unimpaired mutation carriers and 37 non-carrier family members from the Colombia-Boston (COLBOS) Biomarker Study. Measures included 18F-flortaucipir, 11C-Pittsburgh compound B, Consortium to Establish a Registry for Alzheimer's Disease Word List Learning, Trail Making Test, Geriatric Depression Scale, and Geriatric Anxiety Inventory. We examined group differences in amygdala tau levels (whole amygdala, lateral nucleus and basal nucleus) and analyzed tau associations with disease markers and clinical measures.

Results: Amygdala tau levels were higher in unimpaired carriers compared to non-carriers. Among carriers, the basal nucleus showed a greater tau burden than the lateral nucleus, and tau accumulation correlated with closer estimated age to clinical onset and increased cortical amyloid. Additionally, tau in both the basal and lateral amygdala was associated with poorer working memory, lower executive function and greater depressive symptoms. However, amygdala tau did not correlate with symptoms of anxiety. Notably, tau levels in the basal amygdala differentiated carriers from non-carriers, with higher predictive accuracy when neuropsychiatric measures were included.

Conclusions: These findings suggest that in autosomal dominant AD, tau accumulation in the amygdala begins early in the basal nucleus, while both the basal and the lateral nuclei are associated with early cognitive deficits and depressive symptoms. The nuclei's differential vulnerability to pathology underscores the importance of investigating tau spread within amygdala-associated networks, relative to the early clinical manifestations of AD. This study reinforces the potential of amygdala tau burden as a valuable biomarker for preclinical AD.