A bacteriophage-based platform for early diagnosis of Alzheimers disease

Abstract

[Excerpt] Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting a large proportion of the human population worldwide. One hallmark of AD is the increased deposition of plaques, which consist of amyloid-beta (AB) peptide, a key molecule to cause AD onset and progression. However, it is not AB immobilized in plaques, but in the still-soluble oligomeric/fibrillar form that impairs synaptic function and memory encoding. It is therefore important to develop tools that selectively target AB in oligomeric/fibrillar form, to diagnose and neutralize these detrimental AB-clusters during the early stages of the disease. Homing peptides that selectively recognize AB-oligomers and fibrils have been described: AB30-39, reactive for AB fibrils and AB33-42, reactive to fibrils and oligomers [1]. However, these peptides are unable to cross the blood-brain barrier (BBB) by themselves. To overcome this limitation, viruses became a very interesting tool given their versatility to be modified through genetic or chemical manipulation. Bacteriophages (phages), are viruses that only infect bacteria (a major advantage in terms of safety when therapeutic use in humans is envisaged). M13KE is one of the most widely used phage which has been reported as capable to cross the BBB [2]. [...]