Studies on the role of amino acid stereospecificity in amyloid beta aggregation

Amyloid beta (Aβ) deposition and neurodegeneration are the two related events in the pathogenesis of Alzheimer's disease. Several factors modulate the conformation and physical properties of Aβ, which in turn affects its biological functions. Among these, age-dependent changes in the stereospecificity of the amino acids comprising Aβ is one such factors. In the present study, we investigated the aggregation property of Aβ as a function of the stereospecificity of amino acids comprising the peptide. We carried out our study by comparing the physical properties of Aβ(1-40) all-L and Aβ(1-40) all-D enantiomers using various biophysical techniques. These results indicated that the aggregation and folding parameters of Aβ are stereospecific and the aggregation property strongly depends upon the amino acid sequence and their stereospecificity. This may possibly help to understand the stereospecific role of amino acids comprising Aβ in its aggregation and its relevance to neurodegeneration. © 2007 Humana Press Inc.