Subthreshold Amyloid Predicts Tau Deposition in Aging

Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as positive or negative for biomarkers related to the core pathology of beta-amyloid (A beta). However, the accumulation of A beta begins slowly, years before biomarkers become abnormal. We used longitudinal [C-11] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans (N = 71; mean age 75 years; 35% male). We used [F-18] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample (N = 37). We found evidence for an inverted-U relationship between baseline A beta levels and A beta slope in asymptomatic older adults, suggesting a slowing of A beta accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of A beta predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of A beta increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative.