Fig. 3: Comparison among fluid biomarkers on predicting tau PET positivity in cognitively impaired patients of the BioFINDER-2 cohort.

a,b, Prediction of tau PET positivity in cognitively impaired participants from the BioFINDER-2 cohort (n = 663), using a single-cutoff (a) and a two-cutoffs (b) approach, respectively. In the first approach, the threshold was calculated, maximizing sensitivity and fixing specificity at 90%. In the second approach, the lower threshold was obtained by maximizing specificity with sensitivity fixed at 95%, whereas the upper threshold was obtained by maximizing sensitivity and fixing specificity at 95%. Participants who fall between these two cutoffs were classified in the intermediate group. Dots and error bars represent the actual statistic and 95% CI, respectively. Vertical dashed lines represent the maximal statistical value possible (1). For the intermediate value plots, colored bars represent the actual percentage and the error bar the 95% CI. c, Bootstrapped differences (n = 1,000 resamples with replacement stratifying by the output) between the statistics using plasma %p-tau217 (reference) and CSF biomarkers are shown in c for both single cutoff and two cutoffs. The horizontal dashed line is plotted at zero, representing the lack of difference between plasma and CSF biomarkers. We considered plasma and CSF biomarkers clinically equivalent if the 95% CI of the mean difference included zero. Differences in the number of participants in the intermediate group were scaled to a maximum of 1 to be comparable with the other differences. Dots and error bars represent the mean and 95% CI estimate from a bootstrapped sample. d, Histograms represent the distribution of the data colored by the imaging biomarker status. The vertical black line represents the threshold derived from the first approach (a), and red lines represent the lower and upper thresholds from the second approach (b). Tau PET positivity was assessed using an in-house previously validated threshold (SUVR > 1.32). Three individuals were excluded from the histograms in d (only for visualization purposes) due to very low values of plasma %p-tau217. CSF, cerebrospinal fluid; CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value; SUVR, standardized uptake value ratio.