EVOLUTION OF Aß42 AND Aß40 LEVELS AND Aß42/Aß40 RATIO IN PLASMA DURING PROGRESSION OF ALZHEIMER’S DISEASE: A MULTICENTER ASSESSMENT

Objective: To better understand the seemingly contradictory plasma -amyloid (A ) results in Alzheimer’s disease (AD) patients by using a newly developed plasma A assay, the INNO-BIA plasma A forms, in a multicenter study. Methods: A combined retrospective analysis of plasma A isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Results: Detection modules based on two different amino (N)-terminal specific A monoclonal antibodies demonstrated that A in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low A 42 plasma concentrations. A 40 and A 42 concentrations varied consistently with the ApoE genotype, while the A 42/A 40 ratio did not. Irrespective of the decrease of the A 42/A 40 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). Conclusion: A highly robust assay for repeatedly measuring A forms in plasma such as INNO-BIA plasma A forms might be a useful tool in a future risk assessment of AD.