Plasma Amyloid-beta as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Amyloid-beta (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma A beta as an AD biomarker and its relationship with A beta load and to determine the effect of different assay methods on the interpretation of A beta levels. Plasma A beta(1-40), A beta(1-42), and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, A beta levels were compared to A beta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower A beta(1-42) and A beta(1-42/1-40) ratio were observed in patients with AD and inversely correlated with PiB-PET derived A beta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma A beta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma A beta has diagnostic value in a panel of biomarkers.