Biomarkers

Background: We aimed to validate the ability of Alzheimer's disease plasma biomarkers to predict clinical diagnosis and the ability to predict image-based A/T/N biomarkers positivity in Asian population. We also sought to define the optimal cut point for each biomarker.

Method: 232 participants were enrolled, all of whom underwent ¹⁸F-florbetaben (FBB), ¹⁸F-flortaucipir (FTP) PET, volumetric MRI, and neuropsychological assessments. Their plasma samples, collected at the time of the imaging scans and stored at -80 degrees Celsius, were tested for plasma p-tau217/np-tau217 ratio, p-tau217, Aβ_42/40 ratio, and APS2 score at C2N Diagnostics. FBB and FTP positivity were determined based on the SUVR value through a Gaussian mixture model. The presence of hippocampal atrophy was defined as the mean minus 2 standard deviations of amyloid-negative cognitive unimpaired participants. ROC analysis was conducted to assess the predictive ability and determine the optimal cut-off point.

Result: The ability to predict FBB PET positivity was excellent for p-tau217/np-tau217 ratio, p-tau217, and APS2 (AUC=0.964, 0.963, and 0.958, respectively) while Aβ_42/40 ratio showed lower performance with an AUC of 0.726. The Aβ_42/40 ratio did not have the ability to predict FTP positivity, but p-tau217/np-tau217 ratio, p-tau217, and APS2 all exhibited excellent performance with AUC = 0.926, 0.937, and 0.907, respectively. The Aβ_42/40 ratio also did not have the ability to predict hippocampal atrophy, while p-tau217/np-tau217 ratio, p-tau217, and APS2 demonstrated good performance (AUC=0.809, 0.815, and 0.811, respectively). Similarly, only the p-tau217/np-tau217 ratio, p-tau217, and APS2 had the ability to differentiate clinical diagnosis while Aβ_42/40 ratio failed to distinguish. The AUC-ROC for p-tau217/np-tau217, p-tau217, and APS2 all showed no significant difference in DeLong's test when predicting X Y Z. The optimal cutoffs for predicting amyloid, tau and neurodegeneration by p-tau217/np-tau217 ratio, p-tau217 and APS2 showed increases following the progression of AD.

Conclusion: The plasma biomarker using p-tau217 reflects the clinical status well on its own and is excellent at predicting the positivity of image-based biomarkers and diagnostic performance. Among the image-based A/T/N biomarkers, the predictive power was excellent in the order of A, T, and N. The p-tau217 alone was not inferior to the p-tau217/np-tau217 ratio or APS2.