Figure 2.

CSF phosphorylated-tau predicts tau accumulation in females. (A) Sex-disaggregated linear regression analyses were performed in both TRIAD and ADNI cohorts to examine the differences between sexes in the relationships between CSF phosphorylated tau-181 (p-tau₁₈₁) concentrations and the longitudinal accumulation of neurofibrillary tangles (NFTs), as indicated by changes in tau-PET standardized uptake value ratios (SUVRs). In the TRIAD cohort, two follow-up time points were evaluated. Females displayed positive correlations between baseline CSF p-tau₁₈₁ concentrations and NFT accumulation at both 1-year (P < 0.0001, R² = 0.58) and 2-year (P < 0.0001, R² = 0.56) follow-up visits. In contrast, males only exhibited positive associations at the 2-year follow-up assessment (P = 0.0004, R² = 0.25). In the ADNI cohort, three follow-up time points were assessed. Females demonstrated positive correlations between baseline CSF p-tau₁₈₁ concentrations and NFT accumulation at 2-year (P = 0.0004, R² = 0.21) and 4-year (P = 0.0004, R² = 0.34) follow-up visits. Conversely, males did not exhibit any such associations. (B) Sex-disaggregated voxel-based analyses demonstrated that the concentration of p-tau₁₈₁ in the CSF at the baseline was positively associated with longitudinal NFT accumulation in females. In contrast, males presented almost no association. Images represent voxel-based t-statistical parametric maps overlaid on the structural MRI reference template. Age, APOE ε4 carriage status and pathological status were used as covariates in the models. Results were also corrected for multiple comparisons using a false discovery rate (FDR) cluster threshold of P < 0.001. ADNI = Alzheimer’s Disease Neuroimaging Initiative; L = left; R = right; TRIAD = Translational Biomarkers in Aging and Dementia.