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

• Published in: Communications biology 2024-01, Vol.7 (1), p.134-8, Article 134
• Main Authors: Martins, Ivone M., Lima, Alexandre, de Graaff, Wim, Cristóvão, Joana S., Brosens, Niek, Aronica, Eleonora, Kluskens, Leon D., Gomes, Cláudio M., Azeredo, Joana, Kessels, Helmut W.
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14; 14/10; 631/1647/664/1257; 631/378/1689/1283; Aggregates; Alzheimer Disease; Alzheimer's disease; Amino acids; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloidogenesis; Animal models; Animals; Bacteriophage M13 - metabolism; Biology; Biomedical and Life Sciences; Brain; Brain - metabolism; Hippocampus; Humans; Life Sciences; Mice; Mice, Transgenic; Neurodegenerative diseases; Neurosciences; Oligomers; Peptides; Phages; Presenilin 1; Proteins; Transgenic animals; Transgenic mice; Young adults; β-Amyloid
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-05806-5

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