Plasma p‐tau217, p‐tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study

Figures

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  FIGURE 1. Plasma p‐tau217, p‐tau181, and NfL in different diagnostic groups at baseline, and the correlations with baseline MMSE. In (A–C), ANCOVA and post hoc tests based on estimated marginal means (Bonferroni method for adjusting multiple comparisons) were used to test the difference of plasma biomarkers among baseline diagnostic groups after adjusting for age, sex, years of education, and APOE ε4. *p < 0.05, **p < 0.01, and ***p < 0.001. In (D–F), the β with the 95% confidence interval from the univariate linear regression model indicated the association between baseline biomarkers and baseline MMSE. aMCI‐MD, amnestic mild cognitive impairment‐multiple domains; aMCI‐SD, amnestic mild cognitive impairment‐single domain; ANCOVA, analysis of covariance; APOE, apolipoprotein E; CI, confidence interval; CU, cognitively unimpaired; MMSE, Mini‐Mental State Examination; naMCI‐MD, non‐amnestic mild cognitive impairment‐multiple domains; naMCI‐SD, non‐amnestic mild cognitive impairment‐single domain; NfL, neurofilament light chain.

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  FIGURE 2. Correlations of baseline plasma biomarkers and longitudinal MMSE trajectory. In (A–C), multivariate linear regression model with β was used to assess the association between baseline plasma biomarkers and MMSE declining rate adjusting for age, sex, years of education, and APOE ε4. In (D–F), linear mixed‐effects model was used to fit the association between follow‐up time×quartered biomarker levels and MMSE with individualized random intercept and fixed slope, adjusting for age, sex, year of education, and APOE ε4. The slopes of MMSE decline among four levels were compared. *p < 0.05, **p < 0.01, and ***p < 0.001. The p‐tau217 Q1, < 0.24 pg/mL; Q2, ≥ 0.24 and < 0.31 pg/mL; Q3, ≥ 0.31 and < 0.43 pg/mL; Q4, ≥ 0.43 pg/mL. The p‐tau181 Q1, < 1.47 pg/mL; Q2, ≥ 1.47, and < 1.90 pg/mL; Q3, ≥ 1.90 and < 2.49 pg/mL; Q4, ≥ 2.49 pg/mL. NfL Q1, < 11.75 pg/mL; Q2, ≥ 11.75 and < 15.49 pg/mL; Q3, ≥ 15.49 and < 20.89 pg/mL; Q4, ≥ 20.89 pg/mL. APOE, apolipoprotein E; CI, confidence interval; MMSE, Mini‐Mental State Examination; NfL, neurofilament light chain.

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  FIGURE 3. Associations of plasma p‐tau217, p‐tau181, NfL, and incident dementia/AD. In the multivariate Cox regression model, age, sex, education year, and APOE ε4 were adjusted. The linear trend was tested by entering the median value of each quartile of biomarker concentration as a continuous variable in the Cox regression model. *p < 0.05, **p < 0.01, and ***p < 0.001. The p‐tau217 Q1, < 0.24 pg/mL; Q2, ≥ 0.24 and < 0.31 pg/mL; Q3, ≥ 0.31 and < 0.43 pg/mL; Q4, ≥ 0.43 pg/mL. The p‐tau181 Q1, < 1.47 pg/mL; Q2, ≥ 1.47, and < 1.90 pg/mL; Q3, ≥ 1.90 and < 2.49 pg/mL; Q4, ≥ 2.49 pg/mL. NfL Q1, < 11.75 pg/mL; Q2, ≥ 11.75 and < 15.49 pg/mL; Q3, ≥ 15.49 and < 20.89 pg/mL; Q4, ≥ 20.89 pg/mL. AD, Alzheimer's disease; CI, confidence interval; HR, hazard ratio; NfL, neurofilament light chain.

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  FIGURE 4. Plasma p‐tau217, p‐tau181, NfL, and follow‐up Aβ‐PET. (A)–(C) showed the concentrations of 10‐year‐ago baseline plasma biomarkers in Aβ negative vs. Aβ positive. (D)‐(F) demonstrated the association between baseline plasma biomarkers and neocortical Aβ SUVR. Pearson's correlation (r) with 95% CI was indicated accordingly. (G) Presented the predictive value of baseline biomarkers for follow‐up Aβ positive. (H) Illustrated the voxel‐wise association of baseline plasma biomarkers with Aβ PET. Colored regions were statistically significant with uncorrected p < 0.001 with a cluster size of k > 100 voxels. *p < 0.05, **p < 0.01, and ***p < 0.001. Aβ, amyloid‐beta; AUC, area under the curve; CI, confidence interval; NfL, neurofilament light chain; PET, positron emission tomography; PPV, positive predictive value; NPV, negative predictive value; SUVR, standardized uptake value ratio.