Abstract
AbstractBackgroundThe formation of isoAsp via spontaneous asparagine (Asn) deamidation or aspartate (Asp) isomerization has been regarded as a molecular clock of aging that significantly correlates with neurodegenerative diseases (NDDs). Our earlier findings established a strong link between isoAsp and Alzheimer’s disease (AD). In this study, we aimed at validating the diagnostic value of blood isoAsp‐related biomarkers for NDD prediction.MethodsThe levels of isoAsp in plasma human serum albumin (HSA) and the immunoglobulin G (IgG) specific against artificially aged HSA were measured in two cohorts by indirect enzyme‐linked immunosorbent assay (ELISA). Cohort 1 contained patients with AD and controls, while Cohort 2 recruited subjects with mild cognitive impairment (MCI), vascular dementia (VD), frontotemporal dementia (FTD), Parkinson disease (PD) and healthy controls. Apart from the memory tests, other plasma biomarkers reported in literature were quantified as well, including amyloid beta (Aβ) peptides Aβ40 and Aβ42, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau 181 (pTau181) protein.ResultsCohort 1 confirmed as expected a significant increase of isoAsp in HSA and reduction of IgG against aged HSA in AD group compared to controls (P < 0.0001). Cohort 2 revealed similar trends in comparisons between controls and subjects of different NDDs (P < 0.05). The most exciting finding was the best performance of isoAsp‐related biomarkers in MCI prediction among all blood biomarkers. In addition, the levels of our biomarkers were strongly associated with the memory test scores (P < 0.01).ConclusionWe demonstrated the diagnostic capacity of isoAsp‐related biomarkers in predicting NDDs at the early stage of disease. The biomarker levels correlated with cognitive decline, supporting their roles in NDD development. However, the specificity of these novel biomarkers seemed to be not limited to AD. Additional longitudinal studies with follow‐up data shall be conducted for validation of these findings.
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