Background Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive novel biomarkers. autoimmunity plays a key role in the pathogenesis of AD. Objective This study aims to screen innovative diagnostic biomarkers for AD from the perspective of autoantibodies. Methods The study consisted of two screening phases and two validation phases. AD serum autoantibody-related biomarkers were discovered and validated using serum samples from four independent cohorts encompassing 241 participants, i.e., AD patients, healthy controls, and other dementia-related diseases. First, to identify biomarkers for AD, a phage displayed random peptide library (Ph.D.12) was applied to screen specific autoantibodies in a total of 71 serum samples from 39 AD patients and 32 healthy controls. After further screening by polypeptide microarray, Then, for validation, three peptides were analyzed in another two independent cohorts, which included AD patients, healthy controls, and other dementia-related diseases, Enzyme-linked immunosorbent assay (ELISA) was finally used to evaluate their sensitivity and specificity for AD diagnosis. Results Our results show that both AD2024Val03, AD2024Val70, and AD2024Val72 showed a statistically significant ability to discriminate AD patients from controls and other dementia-related diseases. Additionally, combination of these three peptides, AD2024Val, could greatly improve the diagnostic performance (AUC is above 0.95, sensitivity ∼100%, specificity ∼79%). Conclusions the peptides we identified could serve as promising blood biomarkers for AD clinical diagnosis, which also might provide new insights into the potential pathogenesis of AD.
Gao et al. (Sun,) studied this question.