Oral treatment with an A beta 42 oligomer modulating D-amino acid peptide improves cognitive behavior of APP/PS1 double transgenic mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, affecting more than 20 million people world-wide. Today, only palliative therapies for AD are available. Several lines of evidence, including genetics, have provided strong evidence for a central role of amyloid-β-peptide (Aβ) in the pathogenesis of AD. Recents studies indicate that soluble Aβ oligomers instead of fibrillar forms are the major toxic species. We successfully tested Aβ binding D-peptides in AD transgenic mouse models regarding their therapeutic properties. Additionally, we used several biophysical methods for the elucidation of the mechanism thereof. We report on a novel D-enantiomeric amino acid peptide which reduces amyloid plaque load and cerebral damage of transgenic mouse models of AD after direct brain application. Additionally, we show that next to plaque load and inflammation reduction, oral application of the peptide improves cognitive performance. We are providing in vitro data suggesting an Aβ42 oligomer modulating activity of D3. The D-enantiomeric peptide D3 is able to modulate Aβ42 oligomers in vitro. Regardless of its in vivo mechanism of action, D3 exerts therapeutically interesting activities.