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. 2024 Jun 18;30(6):1771–1783. doi: 10.1038/s41591-024-02937-4

Fig. 5. 3R/4R tau ratio in plasma sEVs in the Sant Pau cohort.

Fig. 5

a, Stratified by clinical diagnosis. Horizontal lines indicate the median and IQR. Kruskal–Wallis test with Dunn’s correction for multiple comparisons. HC versus bvFTD P = 0.000009, HC versus PSP P = 0.000007, ALS versus bvFTD P = 0.0000091, ALS versus PSP P = 0.0000016, ALS–FTD versus bvFTD P = 0.0000074, ALS–FTD versus PSP P = 0.0000041, bvFTD versus PSP P = 0.000006; ****P < 0.00001. Biologically independent samples: HC n = 50, ALS n = 65, ALS–FTD n = 58, bvFTD n = 50 (+23 mutation carriers), PSP n = 41. b,c, sEV 3R/4R tau ratios in plasma-derived sEV in genetic cases from Sant Pau cohort (n = 34 genetic cases) stratified by clinical diagnosis (b), HC versus bvFTD P = 0.000009, HC versus PSP P = 0.000007, ALS versus bvFTD P = 0.0000091, ALS versus PSP P = 0.0000016, ALS–FTD versus bvFTD P = 0.0000074, ALS–FTD versus PSP P = 0.0000041, bvFTD versus PSP P = 0.000006; ****P < 0.00001; and stratified by associated molecular pathology and independent from clinical diagnosis (c). The long horizontal line represents the median and the short horizontal lines represent the IQR. Kruskal–Wallis test with Dunn’s correction for multiple comparisons. HC versus TDP-43 P = 0.758, HC versus non-tau/non-TDP-43 P = 0.632, TDP-43 versus non-tau/non-TDP-43 P = 0.425; NS, not significant. TDP-43 pathology group: bvFTD (C9orf72 (n = 12), GRN (n = 6), TARDP (n = 1), VCP (n = 1), TBK-1 (n = 3)); ALS (C9orf72 (n = 3)); ALS–FTD (C9orf72 (n = 1)). Non-tau/non-TDP-43 pathology group: ALS (SOD-1 (n = 3)); FUS (n = 3); ALS–FTD (SOD-1 (n = 1)). d,e, Correlation matrix depicting results of two-sided Spearman correlations in the PSP group, visualized by plotting strength of correlation (r) as a heat map (d) along with P values (e). f,g, Correlation matrix depicting results of two-sided Spearman correlations in the bvFTD group, visualized by plotting strength of correlation (r) as a heat map (f) along with P values (g). h, TDP-43 levels in plasma sEV of the Sant Pau cohort stratified by clinical diagnosis. The long horizontal line represents the median and the short horizontal lines represent the IQR. Kruskal–Wallis test with Dunn’s correction for multiple comparisons. HC versus ALS P = 0.0000075, HC versus ALS–FTD P = 0.0000046, ALS versus bvFTD P = 0.00074, HC versus PSP P = 0.578, ALS versus bvFTD P = 0.000009, ALS versus PSP P = 0.000007, ALS–FTD versus bvFTD P = 0.0000043, ALS–FTD versus PSP P = 0.0000055, bvFTD versus PSP P = 0.0005; *P < 0.05, **P < 0.001, ***P < 0.0001, ****P < 0.00001. Biologically independent samples: HC n = 50, ALS n = 65, ALS–FTD n = 58, bvFTD n = 50 (+23 mutations), PSP n = 41. i,j, Plasma sEV TDP-43 concentrations in genetic cases of the Sant Pau cohort (n = 34 genetic cases) stratified by clinical diagnosis (i), HC versus ALS P = 0.0000075, HC versus ALS–FTD P = 0.0000046, ALS versus bvFTD P = 0.00074, HC versus PSP P = 0.578, ALS versus bvFTD P = 0.000009, ALS versus PSP P = 0.000007, ALS–FTD versus bvFTD P = 0.0000043, ALS–FTD versus PSP P = 0.0000055, bvFTD versus PSP P = 0.0005; and stratified by molecular pathology, independent of clinical diagnosis (j). The long horizontal line represents the median and the short horizontal lines represent the IQR. Kruskal–Wallis test with Dunn’s correction for multiple comparisons. HC versus TDP-43 P = 0.0000063, HC versus non-tau/non-TDP-43 P = 0.541, TDP-43 versus non-tau/non-TDP-43 P = 0.0000051; ****P < 0.00001. TDP-43 pathology group: bvFTD (C9orf72 (n = 12), GRN (n = 6), TARDP (n = 1), VCP (n = 1), TBK-1 (n = 3)); ALS (C9orf72 (n = 3)); ALS–FTD C9orf72 (n = 1). Non-tau/non-TDP-43 pathology group: ALS (SOD-1 (n = 3); FUS (n = 3)); ALS–FTD (SOD-1 (n = 1)). k,i, Correlation matrix depicting results of two-sided Spearman correlations in the ALS group, visualized by plotting strength of correlation (r) as a heat map (k) along with P values (i). ALS-FRS (sEV: r = −0.212), P = 0.015 and time since diagnosis/disease duration (sEV: r = 0.514, P = 0.0004). n,m, Correlation matrix depicting results of two-sided Spearman correlations in the ALS−FTD group, visualized by plotting strength of correlation (r) as a heat map (m) along with P values (n). ALS-FRS (sEV: r = −0.702), P = 0.0002 and time since diagnosis/disease duration (sEV: r = 0.445, P = 0.0005); MMSE (sEV: r = −0.535, P = 0.018).