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

One hallmark of Alzheimer's disease (AD) is the accumulation of amyloid beta (Abeta) peptides in the brain; Abeta mainly consists of 42-mer and 40-mer peptides (Abeta42 and Abeta40). Abeta42 plays a more critical role in the pathogenesis of AD because Abeta42 aggregates much faster and is more toxic than Abeta40. Therefore, there is an urgent need to elucidate the mechanism of aggregation and neurotoxicity of Abeta42 to develop therapeutic agents. Here, we introduce the pathological role of Abeta42 in AD and review our recent findings of the structural analysis of Abeta42 using systematic proline replacement, electron spin resonance and solid-state nuclear magnetic resonance, and the new mechanism of neurotoxicity of Abeta42 through the formation of radicals.