Diagnostic performance of automated plasma amyloid-β assays combined with pre-analytical immunoprecipitation

Background: Measurements of the amyloid-beta (A beta) 42/40 ratio in blood plasma may support the early diagnosis of Alzheimer's disease and aid in the selection of suitable participants in clinical trials. Here, we compared the diagnostic performance of fully automated prototype plasma A beta 42/40 assays with and without pre-analytical sample workup by immunoprecipitation. Methods: A pre-selected clinical sample comprising 42 subjects with normal and 38 subjects with low cerebrospinal fluid (CSF) A beta 42/40 ratios was studied. The plasma A beta 42/40 ratios were determined with fully automated prototype Elecsys (R) immunoassays (Roche Diagnostics GmbH, Penzberg, Germany) by direct measurements in EDTA plasma or after pre-analytical A beta immunoprecipitation. The diagnostic performance for the detection of abnormal CSF A beta 42/40 was analyzed by receiver operating characteristic (ROC) analysis. In an additional post hoc analysis, a biomarker-supported clinical diagnosis was used as a second endpoint. Results: Pre-analytical immunoprecipitation resulted in a significant increase in the area under the ROC curve (AUC) from 0.73 to 0.88 (p = 0.01547) for identifying subjects with abnormal CSF A beta 42/40. A similar improvement in the diagnostic performance by pre-analytical immunoprecipitation was also observed when a biomarker-supported clinical diagnosis was used as a second endpoint (AUC increase from 0.77 to 0.92, p = 0.01576). Conclusions: Our preliminary observations indicate that pre-analytical A beta immunoprecipitation can improve the diagnostic performance of plasma A beta assays for detecting brain amyloid pathology. The findings may aid in the further development of blood-based immunoassays for Alzheimer's disease ultimately suitable for screening and routine use.