Spatiotemporal dynamics of tau extent and load increase in Alzheimer's disease across four longitudinal cohorts.

This longitudinal study including four independent cohorts assessed the spatiotemporal dynamics of tau extent and load changes in Alzheimer's disease using tau positron emission tomography data from 2,459 participants, including 898 followed for up to 7 years. Regional standardized uptake value ratios indexed tau load, whereas the spatial extent of tauopathy (SEOT) (proportion of abnormal voxels) measured tau extent. We observed burden-dependent longitudinal dynamics of tau progression: SEOT showed greater sensitivity to increases over time in regions with low baseline tau burden, whereas the standardized uptake value ratio was more informative for tracking accumulation once regional burden was established. This pattern was consistent across Braak regions and cohorts and was reflected in differential associations with other Alzheimer's disease severity markers. These findings refine models of tau propagation by suggesting that tau positron emission tomography changes may be differentially captured by extent-based and load-based metrics at different stages of disease progression, highlighting SEOT as a promising surrogate outcome for trials.