Neurodegenerative diseases associated antibody repertoire signatures in mimotope arrays based on cyclic versus linear peptides

The role of peptide probes’ conformational flexibility in extracting immunosignatures has not been sufficiently studied. Immunosignatures profile the antibody diversity and prove promising for early cancer detection and multi-disease diagnostics. A novel tool for modeling antibody repertoires, the concept of antibody reactivity graphs, proved instrumental in this respect. Serum samples from patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia of unknown etiology (DUE), and healthy controls were probed using a set of 130 7-mer peptides relevant to neurodegenerative diseases. Results show that linear peptides probed with IgM yielded higher graph density compared to IgG, indicating different levels of polyspecificities. Additionally, the impact of peptide topology and antibody isotype on feature selection was studied using recursive feature elimination. Findings reveal that IgM assays on linear peptides offer superior diagnostic differentiation of neurodegenerative diseases and define the degree of agreement between IgG and IgM immunosignatures with linear or cyclic peptides.