RESUMO
Several lines of evidence suggest that the amyloid-ß-peptide (Aß) plays a central role in the pathogenesis of Alzheimer's disease (AD). Not only Aß fibrils but also small soluble Aß oligomers in particular are suspected to be the major toxic species responsible for disease development and progression. The present study reports on in vitro and in vivo properties of the Aß targeting d-enantiomeric amino acid peptide D3. We show that next to plaque load and inflammation reduction, oral application of the peptide improved the cognitive performance of AD transgenic mice. In addition, we provide in vitro data elucidating the potential mechanism underlying the observed in vivo activity of D3. These data suggest that D3 precipitates toxic Aß species and converts them into nonamyloidogenic, nonfibrillar, and nontoxic aggregates without increasing the concentration of monomeric Aß. Thus, D3 exerts an interesting and novel mechanism of action that abolishes toxic Aß oligomers and thereby supports their decisive role in AD development and progression.