Hyemin Jang, Spain
Samsung Medical Center NeurologyPresenter of 2 Presentations
PERFORMANCE OF AΒ42/AΒ40 RATIO, MEASURED WITH A NOVEL HPLC-MS/MS METHOD IN HUMAN PLASMA, AS A BIOMARKER OF PET STATUS IN A DPUK-KOREAN COHORT.
Abstract
Aims
To assess the feasibility of Aβ42/Aβ40 ratio, measured by a novel HPLC-MS/MS method, as a useful and cost-effective biomarker of PET status in a large Korean cohort from the DPUK Study.
Methods
580 participants were included in six groups: ADD (Alzheimer´s Disease Dementia), AMCI (Alzheimer´s Mild Cognitive Impairment), OC (Old Controls), SVCI (Subcortical Vascular Cognitive Impairment), and CAA (Cerebral Amyloid Angiopathy). Aβ40 and Aβ42 plasma levels were quantitated using a new antibody-free, liquid chromatography-mass spectrometry method (HPLC-MS/MS), which drastically reduces sample preparation time and cost. Receiver Operating Characteristic (ROC) curves were built according to Centiloid-based positivity. Several statistical models were evaluated.
Results
Aβ42/Aβ40 ratios were statistically lower for PET positive individuals in ADD, AMCI, OC (p<0.001) and SVCI groups (p=0.034) but not in CAA group (p=0.544). ROC curves are presented for the total group (n=562, age over 45), which includes ADD (n=131), AMCI (n=212), OC (n=149), SVCI (n=58), and CAA (n=12). Model 1 (Aβ42/Aβ40 ratio) and Model 2 (Aβ42/Aβ40 ratio + ApoE4 + age + diagnosis) are compared. Area Under the ROC Curve (AUC) values for PET positivity based on Centiloid cut-off were 0.808 and 0.871 for Model 1 and Model 2, respectively (p between models=0.002).
Conclusions
Aβ42/Aβ40 ratio in human plasma, measured by this novel HPLC-MS/MS method, showed good discriminating performance based on PET positivity, as demonstrated in this study that contains the largest series of patients being analyzed with this methodology.