Amyloid beta-peptide aggregation. What does it result in and how can it be prevented?

Abstract

Polymerisation of the amyloid beta-peptide (Abeta) gives rise to oligomers and amyloid fibrils, processes that generate cytotoxic assemblies and are associated with neuronal dystrophy and development of Alzheimer's disease. The relationship between Abeta aggregation and the development of Alzheimer's disease has resulted in immense efforts to find ways to prevent it. In spite of this, therapeutic approaches with proven clinical efficacy remain to be identified. The lack of success so far probably stem from a combination of factors. The details of the Abeta aggregation process (es) are not known, in particular several oligomeric forms have been identified but are not yet defined at a molecular level, Abeta is structurally polymorphic which complicate identification of compounds that bind selectively and strongly, and it is not settled which Abeta species is the main disease causing agent. Herein we review current knowledge about monomeric, oligomeric and polymeric Abeta, and discuss ongoing attempts to identify aggregation inhibitors and problems associated therewith.