Takuya Iino, Japan
Sysmex Corporation Central Research LaboratoriesAuthor Of 1 Presentation
A FULLY AUTOMATED PLASMA ABETA ASSAY INCORPORATING APOE4 STATUS PREDICTS AMYLOID POSITIVITY DETERMINED BY A CENTILOID THRESHOLD OF AMYLOID PET
Abstract
Aims
Amyloid pathology is a defining feature of Alzheimer’s disease (AD). Amyloid positron emission tomography (PET) is used to assess amyloid pathology, but its use may be limited by cost and accessibility. Recently, we developed plasma Aβ1-40 and Aβ1-42 immunoassays on our fully automated system (HISCLTM series). Here, we evaluated the performance of our plasma immunoassay to predict amyloid positivity defined by a centiloid threshold.
Methods
149 samples were assessed from the Eisai Elenbecestat Phase 3 program who underwent amyloid PET. The centiloid cut point of 32.20 was determined by predicting amyloid positivity defined by visual read and maximizing the Youden index. To assess the overall performance of plasma Aβ1-42/Aβ1-40 ratio, area under the curve (AUC) was obtained by performing receiver operating characteristic (ROC) analysis using logistic regression. The model incorporating APOE4 status was also evaluated. Furthermore, correlation between plasma Aβ1-42/Aβ1-40 ratio and centiloids was assessed.
Results
The plasma Aβ1-42/Aβ1-40 ratio predicted amyloid PET positivity with an AUC of 0.82 and a sensitivity and specificity equal to 78%. Including APOE4 status as a predictor increased the overall performance (AUC = 0.87), and the sensitivity and specificity were 94% and 71%, respectively. The plasma Aβ1-42/Aβ1-40 ratio was also found to correlate with centiloids values (Spearman rank correlation coefficient = -0.57).
Conclusions
We have observed plasma Aβ1-42/Aβ1-40 ratio can predict amyloid pathology. Incorporating APOE4 status in addition to plasma Aβ1-42/Aβ1-40 ratio achieved high predictive performance, with a high sensitivity. To further assess clinical utility of our assay system, additional sample sets will be evaluated.