The speed limits of tau spreading: The contribution of regional amyloid and education

Abstract Background Here, we investigated the contribution of education and regional amyloid as potential de‐ accelerators in spread tau pathology. Method 85 amyloid‐positive subjects (age=76.80±1.08, education=16.70 ±.50 years, M/F=42/43) were included, for whom [18F]AV‐1451 PET at two timepoints, baseline [18F]AV‐45 PET, ApoE‐status clinical information available ADNI. PETs intensity‐standardized (reference: inferior cerebellum) z‐transformed (control sample: 35 amyloid‐negative subjects). Baseline follow‐up tau‐PET z‐maps converted to volume‐maps (z‐score threshold > 1.96). Based on these volume‐maps, tau‐changes over time assessed: 1) speed (i.e. newly affected volume follow‐up), 2) level rise increase previously volume). These dependent variables used regression analyses including education, global amyloid, tau, ApoE, cognitive function, sex, age predictors. Additionally, amyloid‐burden was regionally correlated 32 Freesurfer‐ROIs with tau‐affected mean z‐score change five Meta‐ROIs (entorhinal cortex, inferior‐temporal, precuneus, middle‐occipital, oribito‐frontal), correcting multiple comparisons. Result Education contributed decelerator ( β=‐.322, p=.037 ), whereas β=.262, p=.029 ) β=.283, p=.028 facilitated speed. Tau positively associated β=‐.211, p=.017 β=.710, p<.001 ). precuneus related greater cingulate amyloid‐burden, temporal, parietal occipital regions orbito‐frontal amyloid‐burden. Conclusion A combination accelerating factors dissociations likely contribute temporo‐spatial evolution