Fig 2: Tau inhibits the binding of Aβ1–42oligomers to 4G8 antibody. Preformed Aβ1–42 oligomers (100 μM) were diluted to 1 μM in 10 mM PBS, pH 7.4 containing 0, 3, 10, 30, and 100 nM tau, incubated for 10 min and injected into an surface plasmon resonance (SPR) apparatus for 120 s over immobilized anti-Aβ 4G8 antibody. A, tau concentration-dependent SPR signal. The sensorgram has two components; the fast-dissociating monomer, which is completely removed at the end of the dissociation (difference between SPR value at t = 120 s and t = 785 s) and the slow-dissociating oligomers (SPR value at t = 785 s). B, tau concentration–dependent SPR signals attributed to Aβ1–42 monomers (red) and Aβ1–42 oligomers (green). The IC50 is 3.9 nM. Aβ, amyloid-beta.

Fig 3: Verification of the predictive performance and clinical applicability of the nomogram for differentiating aMCI and AD. A nomogram outperforms total Tau and Clinical model for predicting the probability of AD in discovery cohort [(A) 0.813 vs. 0.670 and 0.722, P < 0.05] and validation cohort [(B) 0.754 vs. 0.652 and 0.706, P < 0.05]. Calibration curves of three models in discovery cohort (C) and validation cohort (D). Decision curves analyses of three models in discovery cohort (E) and validation cohort (F). Clinical impact curves of nomogram model in discovery cohort (G) and validation cohort (H).

Fig 4: Statistical performance and clinical application of the nomogram. (A) Novel nomogram outperforms total Tau in plasma and Clinical model for discriminating AD patients and non-MCI participants in discovery cohort [(A) 0.960 vs. 0.799 and 0.908, P < 0.05] and validation cohort [(B) 0.938 vs. 0.772 and 0.912, P < 0.05]. Cross-validated calibration curves of the three models in discovery cohort (C) and validation cohort (D). Decision curve analysis demonstrating the net benefit associated with using the novel nomogram in discovery cohort (E) and validation cohort compared to total and Clinical model (F). Clinical impact curves of the nomogram model in discovery cohort (G) and validation cohort (H). The red curve (number of high-risk participants) indicates the number of people who are identified as AD (high risk) by the nomogram at each threshold probability; the blue curve (number of high-risk with event) is the number of true diagnoses at each threshold probability.

Fig 5: The performance of CLIA for total Tau. (A) A quantification of total Tau using developed CLIA. The inset shows a dynamic linear range of Tau concentrations from 7.80 to 250 pg/mL. The repeatability was determined at three standard Tau concentrations: (B) 10 pg/mL; (C) 50 pg/mL; (D) 100 pg/mL. (E) Overall landscape of the three concentrations. The error bars expose the standard deviation.