Fig. 3

‘Core markers’ protein cluster in the TRIAD, EMIF and iNPH cohorts. A Volcano plot showing proteins significantly increased (log₂FC > 0, P < 0.05) and decreased (log₂FC < 0, P < 0.05) in A+T- compared with A-T- individuals in the TRIAD cohort, stratified based on Aβ and tau PET status. Abundance differences were evaluated by fitting linear models, adjusting for age and sex as covariates. Unadjusted P-values were plotted. The dot size shows whether the significance threshold of P < 0.05 was passed after multiple testing correction by the Benjamini–Hochberg procedure. Proteins are color-coded according to their cluster membership (light gray = no cluster membership) (B) Boxplot of ‘Core markers’ Eigenprotein values across controls and Braak stages I-VI in the TRIAD cohort. The protein abundance trend was modelled by a loess-function (shaded area represents the 95% confidence interval). C Boxplot of ‘Core markers’ Eigenprotein values across clinical groups, stratified by Aβ PET status, in the TRIAD cohort. D Proteins with a correlation coefficient ρ > 0.6 with the cluster’s Eigenprotein value, i.e. proteins belonging to the ‘Core markers’ cluster. E Boxplot of ‘Core markers’ Eigenprotein values across clinical groups, stratified by CSF Aβ status, in the EMIF cohort. F Boxplot of ‘Core markers’ Eigenprotein values across cortical biopsy groups in the iNPH cohort. G Boxplot of ‘Core markers’ Eigenprotein values across Aβ-scores, a semiquantitative scale for the Aβ plaque load in the frontal cortex of patients in the iNPH cohort. A gray-colored point indicates the presence of neurofibrillary tangles in the cortical sample of the respective individual. Eigenprotein values of all plots were z-scored to their respective controls. Statistical significances for all boxplots were assessed using linear models, with age and sex as covariates, followed by post-hoc Tukey’s HSD for pairwise comparisons to control the family-wise error rate. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Abbreviations: CTRL, control; CU/SCI, cognitively unimpaired/subjective cognitive impairment; MCI, mild cognitive impairment; AD, Alzheimer’s disease; A-, Aβ-negative; A + , Aβ-positive