Tau spreading precedes the increase in tau load in Alzheimer’s disease
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Tau pathology spreads and accumulates during Alzheimer’s disease (AD), but the relationship between these processes throughout disease progression remains unclear. We assessed the spatiotemporal dynamics of tau spreading and accumulation using tau-PET data from 1,175 participants in the TRIAD and ADNI cohorts, including 277 with 2-year follow-ups. Tau standardized uptake value ratios (SUVR) indexed tau load, while the spatial extent of tauopathy (SEOT; proportion of abnormal voxels) measured tau spread. Longitudinal analyses showed that tau spreading preceded increases in tau load, particularly in regions with low baseline tau levels. Our findings support a sequential model of tau progression: an initial spreading phase, primarily captured by SEOT, followed by an accumulation phase largely reflected by SUVR. These results provide new insights into the pathological mechanisms underlying tau deposition and highlight tau spread as a promising surrogate outcome for clinical trials targeting early-stage AD.
