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The Tau MeTeR composites for the generation of continuous and categorical measures of tau deposits in the brain

Villemagne VL, Doré V, Bourgeat P, Burnham S, Mulligan R, Laws S, Fripp J, Cummings T, Salvado O, Masters CL, Rowe CC

Background: It has been postulated that tau stereotypically spreads from the mesial temporal lobe (MTL) into neo-cortex and that tau deposition restricted to MTL might be just part of the ageing process, suggesting that both the amount and the location of these tau deposits are likely to be relevant for disease staging, prognosis, and progression. We implemented a stereospecific approach to generate both continuous and categorical measures that reflect tau spreading and deposition in order to make results from tau imaging studies clinically relevant and easy to interpret. Methods: Sixty-three participants underwent tau and A? imaging with 18F-AV1451 and 18F-florbetapir (53-HC and 10-AD), while 27 received 18F-THK5317 and 18F-flutemetamol (22-HC and 5-AD). Three regional tau-masks were constructed: Mesial-temporal (Me) comprising entorhinal cortex, hippocampus, parahippocampus and amygdala; Temporoparietal (Te) comprising inferior temporal, fusiform, supramarginal and angular gyri, posterior cingulate/precuneus, superior and inferior parietal, and lateral occipital; and rest of neocortex (R) comprising dorsolateral and ventrolateral prefrontal, orbitofrontal, gyrus rectus, superior and middle temporal, and anterior cingulate. A neocortical tau burden was determined by averaging Te and R. Thresholds were established for each region and tracer. Z-scores were generated for each tracer to allow combination of the results. As continuous variable, a region was deemed high tau when above the 90% ile of the HC. Categorically, a study was deemed high tau when 2 of 3 regions showed high tracer retention. Results: A categorical classification derived from continuous or Z-score data, yielded similar classification than obtained by applying the MeTeR scale. There were differences in the performance of the MeTeR approach between the two tracers. High cortical tau was associated with high A?. Conclusion: We have developed a scale that accounts for the particularities of tau deposition, yielding both regional and global continuous and categorical measures of tau burden in the brain that can be applied to different tau tracers.