A preliminary electron microscopic investigation into the interaction between Aβ_1-42 peptide and a novel nanoliposome- coupled retro-inverso peptide inhibitor, developed as a potential treatment for Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative condition that results in severe cognitive and functional decline in sufferers and for which there are currently no effective treatments to halt or reverse disease progression. AD is the most common form of dementia and age is the major risk factor for this disease. With worldwide population structures changing as increasing number of individuals survive into old age, there is urgent need for novel disease modifying treatments for this condition, which has profound effects upon sufferers in addition to those around them. Some of us have previously developed a peptide inhibitor of Aβ_1-42 aggregation (RI-OR2-TAT) that has been shown to reduce Aβ_1-42 pathology in vivo in mouse models of AD. ∼1690 copies of RI-OR2-TAT have been covalently attached to nanoliposome carrier particles forming Peptide Inhibitor NanoParticles (PINPs), and this study investigated the effect of PINPs upon Aβ_1-42 aggregation at the molecular level. Our results show that PINPs are able to reduce Aβ_1-42 aggregation and do so by binding early (oligomers) and late (fibrillar) stage aggregates. These results highlight the ability of PINPs to disrupt the formation of multiple Aβ_1-42 aggregates capable of causing neurotoxicity and thus provide a strong case for PINPs to be carried forward into early stage clinical trials as a novel therapeutic option for the treatment of AD. (paper)