High‐performance plasma proteomic biomarker candidates in early Alzheimer's disease

Abstract Background The present study aimed to establish a panel of plasma proteins that are associated with cognitive performance and amyloid‐β burden and establish their utility for distinguishing early Alzheimer’s disease (AD) from healthy controls. Method Plasma from fifty patients with early AD (all amyloid‐positive) and forty‐nine healthy controls (HCs) were assayed using quantitative mass spectrometry. The weighted correlation network analysis (WGCNA) was used to explore the association between plasma protein levels and cognitive performance and filter out the high‐performance plasma proteomic biomarker candidates. Further correlation analysis was used to examine these proteins’ association with amyloid‐β burden in AD brain measured with PET imaging. Result We identified 1124 proteins that were dysregulated in AD plasma. Further, 22 panel proteins representative of the AD plasma protein profile were selected based on their association with the cognitive performance and cerebral regional SUVR of PiB‐PET imaging. The panel proteins, involved in the amyloid‐β protein production, metabolism and immune processes, have demonstrated high performance in distinguishing between early AD and HCs. Conclusion This study comprehensively profiled the AD plasma proteome and identified 22 dysregulated proteins as high‐performance biomarker candidates for early Alzheimer’s disease.