Measuring in-vivo tau pathology in the basal forebrain with PET imaging

The basal forebrain (BF) is a site of early tau pathology deposition, and BF cholinergic neurons selectively degenerate in patients with Alzheimer's disease (AD). PET imaging of AD pathology has helped to establish the relationships between early tau in the medial temporal lobe (MTL), amyloid (Aβ) pathology, brain structure and cognition, but it is not clear if PET imaging can be used to similarly characterize early tau pathology in the BF. Here we aim to test the feasibility of measuring tau pathology in the BF in unimpaired older adults with two PET tracers, [¹⁸F]flortaucipir (FTP) and [¹⁸F]MK6240, that have unique properties including distinct off-target signal (OTS) patterns. 1397 unimpaired older adult participants with either FTP (n = 509; Berkeley Aging Cohort Study, ADNI) or MK6240 (n = 888; POINTER Imaging study) scans were included and used to quantify tau-PET signal in three ROI categories: the BF, typical temporal tau-PET ROIs (entorhinal cortex [ERC], temporal MetaROI) and OTS ROIs that are adjacent to the BF (thalamus, pallidum). BF and temporal tau burden were associated with global Aβ burden, but OTS was not. BF and MTL tau showed similar associations with age, BF volume, hippocampal volume and multi-domain cognition. Associations were consistent in both FTP and MK6240 cohorts. MTL tau was negatively correlated with BF volume in whole-brain morphometry analyses. Our findings suggest that it is feasible to use PET to measure tau signal in the BF in unimpaired older adults.