A phage-based platform to detect amyloid-beta oligomers

Amyloid-beta (A) is a prime suspect to cause Alzheimers disease (AD). A peptides can aggregate into soluble oligomers and fibrils, to finally deposit in insoluble plaques. Even though the plaques are main hallmarks of Alzheimers, before plaque formation, the still-soluble A oligomers and fibrils are the culprits that trigger a loss in synapses and memory dysfunction. However, whereas we are well-able to identify A in plaques, we lack the tools to selectively target oligomeric/fibrillar A in the brain. Peptides with high affinity for A may be the answer to this problem, since they are already known to selectively bind oligomeric and fibrillar A, and even can inhibit A aggregation. However, peptides are very unstable and do not cross the blood-brain barrier (BBB). To overcome these limitations, we have used a M13 filamentous phage as vector to display A-specific peptides. Our results show that these engineered phages efficiently recognized A aggregates in brain samples of AD-model mice and of AD patients. This work demonstrates the unique ability of engineered M13 phages to selectively detect oligomeric/fibrillar A in brain samples, thus having a great potential for application in the diagnostics of early Alzheimers disease.