Disrupting beta-amyloid aggregation for Alzheimer disease treatment

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment, Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (A beta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse A beta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural A beta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with A beta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.