Comparison of quantitative digital and semiquantitative assessments of tau pathology in relation to regional in vivo tau PET.

Quantitative digital image analysis has emerged as a powerful tool for assessing neuropathological burden. Although previous studies have compared quantitative digital and semiquantitative pathology measures, their respective relationships with regionally corresponding in vivo tau PET measures remain poorly characterized. We compared quantitative digital pathology quantification and semiquantitative regional gradings of phosphorylated tau (ptau) immunohistochemical staining and assessed their correlations with regional in vivo [18F]flortaucipir standardized uptake value ratios (SUVRs) in 52 cases from the AVID A16 end-of-life study. Digital pathology quantification and semiquantitative gradings of ptau were strongly correlated across all 19 cortical and mesial temporal regions examined (Spearman's rho range: 0.6-0.9; all P < .0001). Both approaches showed similarly robust associations with regionally corresponding tau PET SUVRs. Direct comparison of matched correlation coefficients revealed stronger PET-pathology associations for the digital quantification in the left amygdala and the inferior parietal lobule. Overall, digital pathology quantification and semiquantitative assessments of ptau pathology yielded highly comparable results, both in the quantification of regional pathology burden and in their relationships with tau PET measures. These findings support the use of digital pathology quantification methods and suggest that semiquantitative pathology gradings remain a valid and informative approach for clinicopathological correlation studies.