We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer's disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) - pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.
For the first-time, these results indicate that specific GI tract microbiome-derived neurotoxins have a strong pathogenic role in eliciting alterations in NF-kB-miRNA-directed gene expression that drives the AD process.
These findings indicate the protective effect of ND against memory deficits and AD-like pathological aberrations probably via modulating NF-kB and STAT3 signaling, effects mediated likely by modulating N-methyl-D-aspartate (NMDA) receptors.
In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells, we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB.
Our data demonstrates a crucial and complex role p50 subunit of NF-κB in brain inflammation, especially in regulating the phenotype of microglia after acute and chronic inflammatory insults relevant to clinical conditions, contributing to both pro-inflammatory and anti-inflammatory responses of microglia, infiltration of leukocytes, and clearance of Aβ in Alzheimer's disease.
The expression level of the NFKB1(p105/50Kd) gene was significantly higher in AD with respect to adult age-matched controls (AA) and was related to the Mini-Mental State Examination (MMSE) score of the same patients.
The amplitudes of the P50 responses to the frequent stimuli and of the P300 responses were significantly higher in the subjects whose relatives had definite AD as compared with the other three groups.