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

TY - JOUR

T1 - M13 phage grafted with peptide motifs as a tool to detect amyloid-β oligomers in brain tissue

AU - Martins, Ivone M

AU - Lima, Alexandre

AU - de Graaff, Wim

AU - Cristóvão, Joana S

AU - Brosens, Niek

AU - Aronica, Eleonora

AU - Kluskens, Leon D

AU - Gomes, Cláudio M

AU - Azeredo, Joana

AU - Kessels, Helmut W

N1 - © 2024. The Author(s).

PY - 2024/1/27

Y1 - 2024/1/27

N2 - 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.

AB - 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.

KW - Humans

KW - Mice

KW - Animals

KW - Amyloid beta-Peptides/metabolism

KW - Amyloid beta-Protein Precursor/metabolism

KW - Bacteriophage M13/metabolism

KW - Alzheimer Disease

KW - Mice, Transgenic

KW - Brain/metabolism

U2 - 10.1038/s42003-024-05806-5

DO - 10.1038/s42003-024-05806-5

M3 - Article

C2 - 38280942

SN - 2399-3642

VL - 7

SP - 134

JO - Communications Biology

JF - Communications Biology

IS - 1

ER -