Detection of amyloid-beta oligomers in early Alzheimer´s disease

• Autor(a) principal: Lima, Alexandre
• Data de Publicação: 2023
• Outros Autores: de Graaff, Wim, Aronica, Eleonora, Azeredo, Joana, Kessels, Helmut W., Martins, Ivone M.
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/1822/83836
• topic: Alzheimer´s disease; Amyloid-beta; Bacteriophages; Oligomers; Diagnostics

Amyloid-beta (A) seems to play a central role in Alzheimers disease (AD) pathology. During disease progression A peptides aggregate into various structures including soluble oligomers and fibrils, which ultimately deposit in the brain as insoluble plaques. While the plaques are a well-known hallmark of AD, recent findings revealed that even before plaque formation the still-soluble A oligomers are already able to impair synaptic function as they trigger synaptic loss and memory dysfunction. Despite our ability to detect A plaques, there is currently a lack of earlier diagnostic tools that can specifically target oligomeric A in the brain. We have resorted to bacterial viruses (bacteriophages phages) as a solution to tackle this problem. These viruses are safe, being used in human applications for over a century, as they have no tropism for mammalian cells. Moreover, they are able to cross the blood-brain barrier. Phages were engineered to display specific peptide motifs to recognize A oligomers. Our results showed that the synthetic phages effectively identified A aggregates in brain samples from AD-model mice and AD patients, underlining their specificity towards oligomeric A. These results demonstrate the promising capabilities of this phage-based tool for the early diagnostics of Alzheimers disease and disease monitorization.