Use of biomarkers and imaging to assess pathophysiology, mechanisms of action and target engagement

Abstract

Multidisciplinary basic research led to an evolving knowledge of the molecular pathogenesis of Alzheimer's disease (AD). These advances have been translated into defined therapeutic concepts and distinct classes of compounds with putative disease-modifying effects that are now being tested in clinical trials. There is a growing consensus that disease-modifying treatments may be most effective when commenced early in the course and progression of AD pathophysiology, before amyloid deposition and neurodegeneration become too widespread. Biological indicators of pathophysiological mechanisms are required to chart and identify AD in the prodromal phase or, preferably, in asymptomatic individuals. Biomarkers are becoming even more important, owing to the challenges in demonstrating efficacy of candidate-drugs that hit pathophysiological targets using clinical and cognitive outcomes in early AD trials with limited duration. Currently, there is emerging consensus that advances in therapeutic strategies for AD that delay predefined milestones or slow the cognitive and disease progression would considerably decrease the expanding global burden of the disease. To effectively test preventive compounds for AD and bring therapy to affected individuals as early as possible there is an urgent need for a concerted collaboration among worldwide academic institutions, industry, and regulatory bodies with the aim of establishing networks for the identification and qualification of multi-modal biological disease markers.