Amygdala tau in preclinical Alzheimer’s disease

Abstract

Abstract Background Post-mortem and neuroimaging studies have established the amygdala as one of the earliest sites of tau deposition and neurofibrillary tangles. We investigated the cognitive and anatomical consequences of amygdala tau levels in healthy, older adults. Method We examined 226 cognitively unimpaired ADNI participants who underwent AV-1451 PET imaging (Aß- = 145, Aß+ = 81). We identified cognitive (memory, executive functioning) and MMSE scores ? as well as neuroanatomical measures ? closest in proximity to participants? respective AV-1451 PET scans (average time differences = 1.87 months, 2.04 months, and 11.05 months respectively). We used a series of linear regression models to explore the cross-sectional relationships between amygdala and entorhinal tau/volume and cognition, as well as that between tau and volume. In a smaller set of 177 individuals, we also examined the extent to which neuropsychiatric symptoms (average time from AV-1451 PET scan = 2.71 years) predicted amygdala tau and volume measures. All models controlled for age, sex, education level, and amyloid status. Models with volumetric measures also controlled for intracranial volume. Result Amyloid-beta positive participants had higher tau levels in both the amygdala and entorhinal cortex (p < 0.001); they also had smaller amygdala volumes than Aß- participants (p < 0.05). Within the Aß+ groups, elevated amygdala tau (only) was associated with lower amygdala volumes (ß=-445.198, p=0.01). Both amygdala (ß=-2.908, p=0.02) and entorhinal tau (ß=-3.347, p=0.02) were significant predictors of MMSE scores, but only in Aß+ participants. Amygdala volume was a significant predictor of memory among Aß+ participants (ß=0.001, p=0.01), and there was a trend towards significance between amygdala volume and executive function (ß=0.001, p=0.07). There were no other significant effects on memory or executive functioning measures. Additionally, we found trend-level inverse relationships between NPI anxiety and amygdala tau (ß= -0.073, p=0.1), as well as NPI anxiety and amygdala volume (ß= -104.975, p=0.06). Conclusion Early amygdala tau is associated with reduced volume as well as worse overall global cognition in individuals thought to be in the preclinical stage of AD (Aß+ normal controls). Anxiety may possibly have a relationship with amygdala tau and volume (suggestively associated with less tau and less volume).