Molecular mechanisms and pathology of Alzheimer's disease as reflected by biological markers
40 slide(s) – 00:25:48– English –2010-09-28
Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer’s disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid beta (Abeta) immunotherapy and secretase inhibition, are now being tested in clinical trials. Diseasemodifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. This presentation covers the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total Tau, phosphorylated tau and the 42 amino acid form of Abeta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. I also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, the presentation outlines the roles of CSF biomarkers in drug discovery and clinical trials, and provides perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.