Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

Cerebrospinal fluid and positron emission tomography biomarkers accurately predict an underlying Alzheimer's disease (AD) pathology; however, they represent either invasive or expensive diagnostic tools. Therefore, a blood-based biomarker like plasma amyloid beta (A beta) that could correlate with the underlying AD pathology and serve as a prognostic biomarker or an AD screening strategy is urgently needed as a cost-effective and non-invasive diagnostic tool. In this paper we review the demographic, biologic, genetic and technical aspects that affect plasma A beta levels. Findings of cross-sectional and longitudinal studies of plasma A beta, including autosomal dominant AD cases, sporadic AD cases, Down syndrome cases and population studies, are also discussed. Finally, we review the association between cerebrovascular disease and A beta plasma levels and the responses observed in clinical trials. Based on our review of the current literature on plasma A beta, we conclude that further clinical research and assay development are needed before measures of plasma A beta can be interpreted so they can be applied as trait, risk or state biomarkers for AD.