PET Tau and Amyloid-β Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers

Background: Combining PET amyloid-beta (A beta) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). Objective: We sought to characterize the relationship between A beta and tau ligands as well as with other measures of pathology. Methods: We conducted a multi-center observational study in early AD (MMSE > 20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of A beta and tau at baseline and 6 months; PET-CT imaging with A beta ([(18F)] AV45) and tau ([(18F)] AV1451) ligands at baseline. Results: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical A beta associated with entorhinal cortex tau while CSF tau/A beta ratio correlated strongly with cortical tau but not A beta. Conclusion: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker-the CSF total tau/A beta ratio.