Impact of chronic inflammation induced by oral or gut bacteria on the integrity of blood-brain barrier and its relationship to Alzheimer’s disease
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Citation
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia, affecting approximately one in nine Americans aged 65 and older. Chronic peripheral inflammatory conditions, such as periodontitis and gut dysbiosis, are increasingly recognized as potential contributors to AD pathogenesis. Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, has been linked to neuroinflammation and cognitive decline, possibly via disruption of the blood-brain barrier (BBB). This study investigated the effects of chronic exposure to lipopolysaccharides (LPS) derived from oral (P. gingivalis) and gut (Escherichia coli) sources on BBB integrity and cognitive function.Male C57BL/6 mice (n=24) were treated with P.g-LPS, E. coli-LPS, or PBS via subcutaneous osmotic pumps over 28 days. Behavioral testing included the Morris Water Maze and Y-Maze Spontaneous Alternation Test. BBB integrity was assessed using Evans Blue dye extravasation, with immunohistochemistry and Western blotting performed to evaluate expression of tight junction proteins ZO-1 and occludin.
Mice exposed to LPS, particularly from P. gingivalis, demonstrated significant cognitive deficits without corresponding increases in BBB permeability. While Western blot analysis indicated a modest reduction in ZO-1 levels in the P.g-LPS group, this did not reach statistical significance.
These findings suggest that cognitive impairment can arise from chronic systemic inflammation even in the absence of gross BBB disruption. This study highlights peripheral inflammation as a potential early target for AD intervention.
Description
2025