Deep Plasma Proteomics-Based Diagnostic Panel for Early Detection of Amnestic Mild Cognitive Impairment

Amnestic mild cognitive impairment (aMCI) is often considered an early clinical stage of Alzheimer's disease (AD), but its subtle presentation leads to infrequent neurological evaluations. Early plasma biomarker screening during routine check-ups in community hospitals could enhance aMCI detection rates. Advances in proteomics, particularly mass spectrometry, have enabled the detection of low-abundance plasma proteins, opening new possibilities for aMCI biomarker identification. This study included 84 participants from the STAR cohort. We utilized deep plasma proteomics to detect low-abundance proteins, enriched with nanoparticle magnetic beads. An early diagnostic model for aMCI was developed through bioinformatics and machine learning, with performance compared to the Simoa assay. We identified 4268 low-abundance plasma proteins and constructed a 12-protein diagnostic panel (AUC = 0.992 in the training set, AUC = 0.933 in the testing set), outperforming the Simoa assay (accuracy: 93.9% vs 24.4%). In conclusion, the 12-protein panel provides a cost-effective method for early aMCI detection, potentially improving screening efficacy.