Serotype b of <i>Aggregatibacter actinomycetemcomitans</i> triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?

Abstract

<b>Introduction:</b> Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer's disease (AD), both highly prevalent pathologies among the elderly. The bacteria <i>Aggregatibacter actinomycetemcomitans</i> (<i>Aa</i>), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). <b>Methods: </b>Here, we determined the effects of purified LPS, from serotypes a, b or c of <i>Aa</i>, on primary cultures of microglia or mixed hippocampal cells. <b>Results: </b>We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ_1-42 peptide. These results indicate that LPS from different <i>Aa</i> serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. <b>Conclusion:</b> Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD.