The turn formation at positions 22 and 23 in the 42-mer amyloid β peptide: The emerging role in the pathogenesis of Alzheimer's disease

Abstract

One hallmark of Alzheimer's disease (AD) is the accumulation of amyloid β (Aβ) peptides in the brain; Aβ mainly consists of 42-mer and 40-mer peptides (Aβ42 and Aβ40). Aβ42 plays a more critical role in the pathogenesis of AD because Aβ42 aggregates much faster and is more toxic than Aβ40. Therefore, there is an urgent need to elucidate the mechanism of aggregation and neurotoxicity of Aβ42 to develop therapeutic agents. Here, we introduce the pathological role of Aβ42 in AD and review our recent findings of the structural analysis of Aβ42 using systematic proline replacement, electron spin resonance and solid-state nuclear magnetic resonance, and the new mechanism of neurotoxicity of Aβ42 through the formation of radicals. © 2010 Japan Geriatrics Society.