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Innovative IgG Biomarkers Based on Phage Display Microbial Amyloid Mimotope for State and Stage Diagnosis in Alzheimer's Disease.
- Source :
-
ACS chemical neuroscience [ACS Chem Neurosci] 2020 Apr 01; Vol. 11 (7), pp. 1013-1026. Date of Electronic Publication: 2020 Mar 24. - Publication Year :
- 2020
-
Abstract
- An innovative approach to identify new conformational antigens of Aβ <subscript>1-42</subscript> 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 Aβ <subscript>1-42</subscript> 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 vitro Aβ <subscript>1-42</subscript> -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.
- Subjects :
- Alzheimer Disease metabolism
Amyloid beta-Peptides metabolism
Amyloidogenic Proteins metabolism
Bacteriophages genetics
Bacteriophages immunology
Bacteriophages metabolism
Humans
Peptide Fragments metabolism
Alzheimer Disease diagnosis
Amyloid metabolism
Biomarkers analysis
Immunoglobulin G metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1948-7193
- Volume :
- 11
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- ACS chemical neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 32176482
- Full Text :
- https://doi.org/10.1021/acschemneuro.9b00549