Investigation for the involvement of microbial FliC and DING proteins in Alzheimer's Disease and Mild Cognitive Impairment and correlation with neurodegeneration and inflammation markers

Abstract

The pathology of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) has been linked to inflammation attributed to the microbiome, mainly originating from the oral cavity and the intestine. The goal of this research was to estimate the levels of the bacterial proteins flagellin (FliC) and bacterial DING in cerebrospinal fluid (CSF) and their correlation with neurodegeneration and inflammation markers. FliC and DING levels were evaluated in CSF of 54 AD and 47 MCI patients compared to 23 cognitively healthy individuals, using indirect ELISA. Correlation and multilinear regression analyses with the inflammatory biomarkers COX-1 and COX-2, and with the AD hallmarks, Αβ42, and tau, were conducted as well. FliC and DING proteins were found increased in the CSF of AD patients compared to the control group, while FliC of MCI patients was also elevated in comparison with controls. In addition, FliC and DING levels correlate with each other, with tau and both COX-1/2. Also, multilinear regression analyses suggest that DING is a significant determinant of FliC in CSF and vice-versa, while COX-2 determines both FliC and DING levels and COX-1 only the levels of DING. Consequently, the increase of bacterial FliC and its possible translocation to the brain is an early event in dementia, reflected in dysbiosis events found in MCI and AD patients, and possibly neuroinflammation and neurodegeneration. Additionally, increased DING in AD patients seems to be a significant part of the inflammatory events and its correlation with FliC points to a possible link between these proteins.