Pro-inflammatory S100A9 protein as a robust biomarker differentiating early stages of cognitive impairment in Alzheimer’s Diseased

Abstract

Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1−42and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer’s disease (MCI-AD), Alzheimer’s disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1−42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCIAD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1−42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from Va