Additional file 1 of CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration
Creators: name: Mravinacová, Sára
name: Alanko, Vilma
name: Bergström, Sofia
name: Bridel, Claire
name: Pijnenburg, Yolande
name: Hagman, Göran
name: Kivipelto, Miia
name: Teunissen, Charlotte
name: Nilsson, Peter
name: Matton, Anna
name: Månberg, Anna
Publisher: name: figshare
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Neuroscience
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Mental Health
subject: Hematology

description: Additional file 1: Supplementary Figure 1. Cohort description based on amyloid and tau CSF levels. Discovery cohort sample classification based on p-tau and Aβ42/40 ratio levels (left); validation cohort sample classification based on p-tau and Aβ42 concentration (right). The dashed lines in both plots mark the cut-off for p-tau (yaxis) and Aβ42/40 or Aβ42 (xaxis) classification.Supplementary Figure 2. Correlation network of the measured proteins in A+T+ individuals. Only correlations with |rho| &gt; 0.5 are visualised in the network. Supplementary Figure 3. Correlation network of the measured proteins in A-T- individuals with SCD. Only correlations with |rho| &gt; 0.5 are visualised in the network. Supplementary Figure 4. Examples of CSF protein level comparison between A-T- (SCD) and A+T+ individuals.(A) Proteins with significantly different levels, (B) proteins with no significant differences between the sample groups. Supplementary Figure 5. Correlation between all measured CSF proteins in A+T+ individuals with SCD. The heatmap is clustered based on correlation between the proteins and annotated with the clustering results from Fig. 1A, based on the correlation of the individual proteins to amyloid, tau and NfL markers in A+T+ individuals, and Spearman’s correlation with albumin CSF/serum quotient (Q-Alb). Supplementary Figure 6. Correlation between all measured CSF proteins in A-T- individuals. The heatmap is clustered based on correlation between the proteins and annotated with the clustering results from Fig. 1A, based on the correlation of the individual proteins to amyloid, tau and NfL markers in A+T+ individuals, and Spearman’s correlation with albumin CSF/serum quotient (Q-Alb). Supplementary Figure 7. Distribution of median ROC AUCs for the protein pairs originating in different clusters in the discovery cohort. The p-values were calculated using the Wilcoxon rank sum two-sided test. Supplementary Figure 8. Association of CSF GAP43 and PTPRN2 to p-tau, Aβ42/40 ratio, age, and sex. Scatterplots showing the correlation between CSF levels of GAP43 and PTPRN2, with the individual data points colored by (A) p-tau (on a logarithmic scale), (B) Aβ42/40 ratio, (C) age at sampling, (D) sex together with AT status. Only A-T- (SCD) and A+T+ individuals are included. Supplementary Figure 9. Distribution of ROC AUCs for the protein pairs originating in different clusters in the validation cohort. The p-values were calculated using the Wilcoxon rank sum two-sided test. Supplementary Figure 10. A heatmap of median ROC-AUC values from SVM models from each protein pair in validation cohort. The heatmap is clustered based on the ROC-AUC results and annotated with clustering results from Fig 1A, based on correlation of the individual proteins to amyloid, tau and NfL markers in A+T+ individuals in discovery cohort. Supplementary Figure 11. Comparison of median model AUC values in discovery and in validation cohort. The plot line is set on parameters: intercept = 0, slope = 1. Supplementary Figure 12. Comparison of correlations of protein pair ratios originating in different clusters to cognitive scores in discovery and validation cohort. The p-values were calculated using the Wilcoxon rank sum two-sided test using absolute correlation values. The stars represent the level of significance measured by the p-value:  ns&gt; 0.05, * &lt; 0.05; ** &lt; 0.01, *** &lt; 0.001, **** &lt; 1e-04. The color of the stars indicates the cluster with stronger correlations. Supplementary Figure 13. Comparison of correlations of single proteins or protein pair ratios to cognitive scores between the different protein pair clusters in discovery and validation cohort. The p-values were calculated using the Wilcoxon rank sum two-sided test using absolute correlation values. The stars represent the level of significance measured by the p-value:  ns&gt; 0.05, * &lt; 0.05; ** &lt; 0.01, *** &lt; 0.001, **** &lt; 1e-04. The color of the stars indicates the cluster with stronger correlations. Supplementary Figure 14. Correlation between cognitive measurements in discovery cohort. Only A-T- individuals with SCD and A+T+ individuals were included. The correlation between the cognitive scores is evaluated using the Pearson’s method. Supplementary Table 1. List of analysed proteins and used antibodies. Supplementary Table 2. Amyloid- and tau- associated proteins and brain-elevation status of their respective genes based on tissue transcriptomic data from the Human Protein Atlas. Supplementary Table 3. Proteins with significantly different CSF levels in A-T- (SCD) and A+T+ sample groups. Supplementary Table 4. Median ROC AUC difference between models with only protein pairs as predictors and models with both protein pairs and albumin CSF/serum ratio as predictors in the discovery cohort. Supplementary Table 5. Pearson correlation between protein pair ratios and cognitive scores in the discovery cohort (top 15). Only A-T- individuals with SCD and A+T+ individuals were included. Supplementary Table 6. Pearson correlation between protein pair ratios and cognitive scores in the validation cohort (top 15).