Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alzheimer's disease (AD). Primarily, the focus has been directed towards brain amyloid pathology and its relation to synaptic and neuronal loss. Clearly, AD is associated with accumulation of amyloid beta (Abeta) in the brain. Further, the results of many experimental studies suggest that certain forms of Abeta may act as initiators in the disease process with potent toxic effects at the synaptic level. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include secreted Abeta and amyloid precursor protein (APP) isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on CSF and plasma Abeta-related biomarkers for AD and how they may reflect pathogenic changes in AD-affected neuronal networks. We also consider their usefulness in clinical practice and in clinical trials.
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