Mesial temporal tau in amyloid-β-negative cognitively normal older persons

Abstract

Background: Tau deposition in the mesial temporal lobe (MTL) in the absence of amyloid-β (Aβ−) occurs with aging. The tau PET tracer 18F-MK6240 has low non-specific background binding so is well suited to exploration of early-stage tau deposition. The aim of this study was to investigate the associations between MTL tau, age, hippocampal volume (HV), cognition, and neocortical tau in Aβ− cognitively unimpaired (CU) individuals. Methods: One hundred and ninety-nine Aβ− participants (Centiloid < 25) who were CU underwent 18F-MK6240 PET at age 75 ± 5.2 years. Tau standardized uptake value ratio (SUVR) was estimated in mesial temporal (Me), temporoparietal (Te), and rest of the neocortex (R) regions and four Me sub-regions. Tau SUVR were analyzed as continuous variables and compared between high and low MTL SUVR groups. Results: In this cohort with a stable clinical classification of CU for a mean of 5.3 years prior to and at the time of tau PET, MTL tau was visually observed in 9% of the participants and was limited to Braak stages I–II. MTL tau was correlated with age (r = 0.24, p < 0.001). Age contributed to the variance in cognitive scores but MTL tau did not. MTL tau was not greater with subjective memory complaint, nor was there a correlation between MTL tau and Aβ Centiloid value, but high tau was associated with smaller HV. Participants with MTL tau had higher tau SUVR in the neocortex but this was driven by the cerebellar reference region and was not present when using white matter normalization. Conclusions: In an Aβ− CU cohort, tau tracer binding in the mesial temporal lobe was age-related and associated with smaller hippocampi, but not with subjective or objective cognitive impairment.