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ACS Chem Neurosci. 2020 Apr 1;11(7):1013-1026. doi: 10.1021/acschemneuro.9b00549. Epub 2020 Mar 24.

Innovative IgG Biomarkers Based on Phage Display Microbial Amyloid Mimotope for State and Stage Diagnosis in Alzheimer's Disease.

Author information

1
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
2
STmicroelectronics, Stradale Primosole, 50, 95121 Catania, Italy.
3
Distretto Tecnologico Micro e Nano Sistemi Sicilia, Strada VII-Zona Industriale, 95121 Catania, Italy.
4
Neurology Clinic, Department "G.F. Ingrassia", Section of Neurosciences, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy.

Abstract

An innovative approach to identify new conformational antigens of Aβ1-42 recognized by IgG autoantibodies as biomarkers of state and stage in Alzheimer's disease (AD) patients is described. In particular, through the use of bioinformatics modeling, conformational similarities between several Aβ1-42 forms and other amyloid-like proteins with F1 capsular antigen (Caf1) of Yersinia pestis were first found. pVIII M13 phage display libraries were then screened against YPF19, anti-Caf1 monoclonal antibody, and IgGs of AD patients, in alternate biopanning cycles of a so-called "double binding" selection. From the selected phage clones, one, termed 12III1, was found to be able to prevent in vitro1-42-induced cytotoxicity in SH-SY5Y cells, as well as to promote disaggregation of preformed fibrils, to a greater extent with respect to wild-type phage (pC89). IgG levels detected by 12III1 provided a significant level of discrimination between diseased and nondemented subjects, as well as a good correlation with the state progression of the disease. These results give significant impact in AD state and stage diagnosis, paving the way for the development not only for an innovative blood diagnostic assay for AD precise diagnosis, progressive clinical assessment, and screening but also for new effective treatments.

KEYWORDS:

AD state and stage progression screening; Aβ1−42 cytotoxicity inhibition; Phage display double binding selection; amyloid conformational epitopes; autoantibody detection; fibril disaggregation

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