INFLUENCE OF ADVANCED GLYCATION END-PRODUCTS AND AGE-INHIBITORS ON NUCLEATION-DEPENDENT POLYMERIZATION OF BETA-AMYLOID PEPTIDE

Nucleation-dependent polymerization of beta-amyloid peptide, the major component of plaques in patients with Alzheimer's disease, is signifi cantly accelerated by crosslinking through Advanced Glycation End-prod ucts (AGEs) in vitro. During the polymerization process, both nucleus formation and aggregate growth are accelerated by AGE-mediated crossli nking. Formation of the AGE-crosslinked amyloid peptide aggregates cou ld be attenuated by the AGE-inhibitors Tenilsetam, aminoguanidine and camosine. These experimental data, and clinical studies, reporting a m arked improvement in cognition and memory in Alzheimer's disease patie nts after Tenilsetam treatment, suggest that AGEs might play an import ant role in the etiology or progression of the disease. Thus AGE-inhib itors may generally become a promising drug class for the treatment of Alzheimer's disease.