Confounding Factors Influencing Amyloid Beta Concentration in Cerebrospinal Fluid

Abstract

Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form ofβ-amyloid (Aβ42). However, a high discrepancy between different centers in measuredAβ42levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measuredAβ42level.Methods. Aliquots of CSF samples were either treated differently prior toAβ42measurement or analyzed using different commercially available xMAP or ELISA assays.Results. Confounding factors affecting CSFAβ42levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification.Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.