Plasma tau/amyloid-β1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease

One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-β1-42. We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-β1-42, and t-tau/amyloid-β1-42 with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-β1-42 in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-β1-42 correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-β1-42. These results indicate that combination of plasma tau and amyloid-β1-42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration.