We detail a cross-sectional, multi-plasma biomarker characterization of the AIBL cohort samples using plasma Aβ42/40 ratio, pTau217, pTau181, GFAP, and Nf-L assays across the Alzheimer’s disease (AD) continuum, and determine discriminatory performance with CNS amyloid PET imaging status.

Lower Lumipulse and Simoa Aβ42/40 ratios were observed in Aβ+ vs Aβ- groups (p<0.0001), with differences across the four clinical subgroups (p <0.0001).  Aβ42/40 ratio ROC-AUC vs amyloid PET status was 0.88 and 0.85, respectively, consistent with moderate Spearman correlations between Aβ42/40 ratios and amyloid PET centiloids (R = -0.53; -0.49, (p<0.0001).  Simoa pTau217 and pTau181 levels were elevated in Aβ+ vs Aβ- groups (p<0.0001), increasing with disease severity (4.0- and 1.9-fold, respectively).  ROC-AUC vs amyloid PET status was 0.95 and 0.81, respectively. Multivariable models combining Lumipulse Aβ42/40 ratio and demographic base model improves the AUC to 0.913, whereas Aβ42/40 + pTau217 + base model results in an AUC = 0.978.

A plasma biomarker study of a clinically well-characterized cohort revealed an improved association of Aβ42/40 ratios and pTau217 levels with CNS amyloid PET, as measured by recently developed immunoassays. These results support further validation toward AD drug development and patient management.