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STAGE-SPECIFIC PREDICTION OF TAU-PET ACCUMULATION USING PLASMA BIOMARKERS
Abstract
Aims
Plasma markers of tau, such as phosphorylated (pTau) or total tau detect the protein levels in the blood. They could potentially be useful in the clinical and clinical trial settings to assess changes in tau over time. Our aim was to investigate whether plasma pTau epitopes and N-terminal tau fragment (NTA) predict future accumulation of tau-PET in specific regions.
Methods
We included cognitively unimpaired, mild cognitive impairment and AD participants from the TRIAD cohort. Tau progression was calculated as the relative change (Δ) in [18F]MK6240. We conducted linear regressions between plasma levels at baseline and Δ[18F]MK6240, in Braak regions I/II, III/IV and V/VI and voxel-wise. Finally, we assessed which plasma marker was the best predictor of tau accumulation at specific Braak stages by comparing β-values of the linear regressions between plasma markers (z-scores) and Δ[18F]MK6240, correcting for age and sex.
Results
We observed a strong correlation between baseline plasma pTau181, 231 and 217 and ΔBraakIII/IV and ΔBraakV/VI, when NTA correlated with ΔBraakV/VI only (Figure1). Voxel-wise analyses showed a positive relationship between Δ[18F]MK6240 and plasma pTau181, 231 and 217 in the superior frontal, orbitofrontal and cingulate cortices. Plasma NTA signal was observed in the cuneus, paracentral and precentral gyri (Figure2). Finally, among the significant associations, the stronger β-value was for plasma pTau231 for ΔBraakIII/IV and plasma NTA for ΔBraakV/VI (Figure3).
Conclusions
Plasma pTau biomarkers(231, 181, 217) are great predictors of future tau accumulation in regions outside of the medial temporal lobe (BraakIII and above), while NTA is related to accumulation at late Braak stages(V/VI). Plasma pTau231 was the best predictor of early tau, while NTA was for late Braak regions. Plasma markers could be useful at predicting future tau accumulation, at a stage-specific level.