Intracerebroventricular Cutibacterium acnes Generates Manifestations of Alzheimer's Disease-like Pathology in the Rat Hippocampus

Abstract

The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid β (Aβ) deposits in the hippocampus; Aβ aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology.