Voxel-wise association analyses showed inverse correlation of the STA and t-tau ratio with regional tau-PET accumulation. The voxel-wise analyses were adjusted for Aβ PET uptake, age, sex and APOE ε4 genotype. The P values for the between-group comparisons can be found in Supplementary Table 4 . This figure, alongside Extended Data Figs. 5 and 6 , demonstrates that there are only minute amounts of STAs in the CSF of young adults and cognitively normal older adults. However, the levels increase with disease severity such that the ratio of these tau forms to t-tau, accounting for interindividual variability in tau production and/or release, decreases with worsening NFT pathology as indexed by the Braak staging both at autopsy using immunohistochemical analysis and in vivo using tau-PET. These changes are specific to individuals with high ADNC with or without mixed neurodegenerative pathologies.
