Biomarkers for Alzheimer's disease

It has been determined that patients suffering from mild cognitive impairment (MCI) may progress to Alzheimer's disease (AD), which offers a window for therapeutic intervention to slow or halt disease progression. Thus, the detection of prodromal AD is essential to initiate early treatment. The key pathologic hallmark of AD is amyloid beta peptide 42 (Abeta(42)). Probably because of its direct contact with brain tissue, levels of Abeta(42) in combination with phosphorylated tau determined in cerebrospinal fluid (CSF) appear to be useful markers of the disease. In addition, structural and functional brain imaging with magnetic resonance techniques and metabolic imaging with positron emission tomography have been shown to provide useful disease markers. These imaging markers include diminished global brain and hippocampus volume, grey matter loss in the mediotemporal lobe, functional neuronal disconnections and regional hypometabolism. To date, the combination of CSF Abeta(42) and tau parameters provide a sensitivity and a specificity of > 80%. In this article we summarize key aspects of diagnostic markers for AD based on published knowledge. We also dwell on the potential usefulness of these markers for treatment monitoring and in the process of developing and evaluating novel drugs.