Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function


  • C. Barucker
  • H.J. Bittner
  • P.K.Y. Chang
  • S. Cameron
  • M.A. Hancock
  • F. Liebsch
  • S. Hossain
  • A. Harmeier
  • H. Shaw
  • F.M. Charron
  • M. Gensler
  • P. Dembny
  • W. Zhuang
  • D. Schmitz
  • J.P. Rabe
  • Y. Rao
  • R. Lurz
  • P.W. Hildebrand
  • R.A. McKinney
  • G. Multhaup


  • Scientific Reports


  • Sci Rep 5: 15410


  • The amyloid-beta42 (Abeta42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Abeta42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Abeta-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Abeta42 oligomers, rather than simply inhibiting the aggregation of Abeta monomers into oligomers. Our data show that AIP diminishes the loss of Abeta42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Abeta42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically "trapping" low-n oligomers provides a novel strategy for toxic Abeta42-oligomer recognition and removal.