M13 phage grafted with peptide motifs as a tool to detect amyloid-β oligomers in brain tissue

Oligomeric clusters of amyloid-beta (A beta) are one of the major biomarkers for Alzheimer's disease (AD). However, proficient methods to detect A beta-oligomers in brain tissue are lacking. Here we show that synthetic M13 bacteriophages displaying A beta-derived peptides on their surface preferentially interact with A beta-oligomers. When exposed to brain tissue isolated from APP/PS1-transgenic mice, these bacteriophages detect small-sized A beta-aggregates in hippocampus at an early age, prior to the occurrence of A beta-plaques. Similarly, the bacteriophages reveal the presence of such small A beta-aggregates in post-mortem hippocampus tissue of AD-patients. These results advocate bacteriophages displaying A beta-peptides as a convenient and low-cost tool to identify A beta-oligomers in post-mortem brain tissue of AD-model mice and AD-patients. Bacteriophages displaying amyloidogenic peptides are able to identify amyloid-beta oligomers in post-mortem brain tissue of APP/PS1-transgenic mice and of Alzheimer patients.