Cognitive‐behavioral associations of amygdala subregional tau pathology in cognitively unimpaired Presenilin‐1 E280A mutation carriers

Abstract

AbstractBackgroundCarriers of the Presenilin‐1 (PSEN1) E280A mutation are virtually determined to develop Alzheimer’s disease (AD) dementia by midlife. Tau pathology accumulates in the amygdala of PSEN1 carriers prior to clinical onset. Amygdala dysfunction, particularly in basolateral regions, may contribute to early neuropsychiatric symptoms in sporadic AD and other dementias. We aimed to examine the cognitive‐behavioral associations of subregional amygdala tau pathology in preclinical PSEN1 carriers, focusing on episodic memory and neuropsychiatric symptoms.MethodsParticipants included 25 unimpaired PSEN1 carriers and 37 non‐carriers from the Colombia‐Boston (COLBOS) Biomarker Study, matched in age, sex, and education (Table 1). In vivo regional tau pathology was measured using PET (Flortaucipir), with lateral and basal (aggregate region comprised of basal and accessory basal nuclei) amygdala as primary regions of interest (automatic segmentation using FreeSurfer v7). Memory was measured using the CERAD Word List Delayed Recall. Neuropsychiatric symptoms were measured using the Geriatric Anxiety Scale (GAI) and Geriatric Depression Scale (GDS). Associations with tau were tested using Spearman correlation. Group differences on cognitive‐behavioral measures were tested using independent samples t‐tests.ResultsCarriers and non‐carriers did not differ in overall depression or anxiety symptoms, but carriers had lower memory recall scores (Table 1). In carriers, lower recall was associated with greater tau accumulation in lateral (r = ‐.422, p = .036) but not basal (r = ‐.291, p = .158) amygdala. Higher depressive symptoms in carriers were associated with greater tau in both lateral (r = .530, p = .007) and basal (r = .467, p = .019) amygdala. Anxiety symptoms were not associated with amygdala tau in carriers (ps > .309). No significant associations were observed in non‐carriers.ConclusionsAmygdala tau pathology is associated with depressive symptoms and lower memory recall in cognitively unimpaired PSEN1 carriers, particularly in lateral amygdala. These results suggest that lateral amygdala tauopathy may be an early indicator of disease progression and may underlie cognitive and neuropsychiatric changes associated with early AD. Future longitudinal studies with larger samples and additional regional tau measures are needed to clarify the effects of subregional amygdala tau pathology on clinical onset and progression of AD.