Engineered M13-bacteriophages to target amyloid- peptide in oligomeric/fibrillar form for Alzheimer´s Disease diagnosis

Abstract

[Excerpt] Alzheimer´s Disease (AD) is an age-dependent neurodegenerative disease with very high incidence worldwide and detrimental consequences. Manifests as a decline in cognitive functions and memory loss, characterized at molecular level by an increased deposition of amyloid-beta (AB) plaques. Nevertheless, it is AB in the still-soluble oligomeric/fibrillar form that impairs synaptic function and memory encoding [1]. Therefore, new tools that selectively target AB oligomers/fibrils in the brain hold great potential to halt AD at an early stage. Specific amyloidogenic peptide motifs grafted into an antibody, were described to react with AB fibrils: AB30-39, and with fibrils and oligomers: AB33-42 [2]. However, the blood-brain-barrier, by sheltering the central nervous system from the systemic circulation, is a major bottleneck for peptide- and antibody-based applications. To overcome this limitation, bacteriophages and phage display can be applied [3,4]. [...]