Biomarkers.

Background: The association between medial temporal and neocortical SUVR depends on availability of cortical tau. However, tracer differences in affinity and off-target binding might interfere in these associations. Here, we examined the association between medial temporal and neocortical SUVR using voxel-based approach.

Method: We included 92 individuals (46 Cognitively Unimpaired and 46 Cognitively Impaired) from the HEAD Study recruited at McGill University. All individuals were assessed for amyloid-β (Aβ) deposition using [F]AZD4694-PET and at least two tau-PET ligands ([F]MK6240 and [F]Flortaucipir). A subset of 25 individuals had 2 additional tau-PETs scans: [F]RO948 and [F]PI-2620. Voxel-based regression models evaluated the relationship between PET tracers' uptake in the entorhinal cortex (EC) and its association with the tracer's uptake in later Braak regions. All models include Aβ-PET, age, and sex as covariates and RFT was used to account for multiple comparisons. Additionally, we extracted the number of significant voxels in the associations within each Braak regions.

Result: Positive associations were observed between tau-PET SUVR in the EC (Figure 1). [F]MK6240 EC was correlated with tracer uptake in the whole cortex. [F] Flortaucipir was associated with tracer uptake in similar regions, albeit showing a lower t-value. [F]PI2620 EC uptake correlated with binding in regions Braak II-V. Finally, [F]RO948 was associated with uptake in regions Braak II-IV. We further validated our results by extracting the number of significant voxels in each Braak regions. [F]MK6240 showed the highest percentage of spatial extent of tau spreading in all Braak regions, followed by [F]Flortaucipir and [F]RO948. [F]PI2620 demonstrated the lowest spatial extent.

Conclusion: [F]MK6240 SUVR better predicted the spatial extent of tau spreading in the whole cortex. Results were concordant at the voxel and region-on-interested levels. [F]Flortaucipir showed similar results, in lower magnitude. Finally, [F]PI2620 and [F]RO948 were further lower. Nevertheless, the later analyses were conducted in a smaller sample. Our results support the concept that MK6240 affinity possibly explain these results.