Evolution of Aβ42 and Aβ40 levels and Aβ42/Aβ40 ratio in plasma during progression of Alzheimer's disease: A multicenter assessment

To better understand the seemingly contradictory plasma β-amyloid (Aβ) results in Alzheimer’s disease (AD) patients by using a newly developed plasma Aβ assay, the INNO-BIA plasma Aβ forms, in a multicenter study. A combined retrospective analysis of plasma Aβ isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Detection modules based on two different amino (N)-terminal specific Aβ monoclonal antibodies demonstrated that Aβ in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Aβ42 plasma concentrations. Aβ40 and Aβ42 concentrations varied consistently with the ApoE genotype, while the Aβ42/Aβ40 ratio did not. Irrespective of the decrease of the Aβ42/Aβ40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). A highly robust assay for repeatedly measuring Aβ forms in plasma such as INNO-BIA plasma Aβ forms might be a useful tool in a future risk assessment of AD.