Pro-inflammatory S100A9 protein as a robust biomarker differentiating early stages of cognitive impairment in Alzheimer's disease.

Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1-42 and tau-proteins. CSF samples from 104 stringently-diagnosed individuals divided in five subgroups were analysed, including non-demented 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 MCI-AD and AD/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 sensitive to 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 VaD.