Bacteria, endotoxins and chronic neuroinflammation: An etiopathogenesis for Alzheimer’s disease?

Abstract

Alzheimer’s disease represents one of the main health problems in advanced countries. Actually, we do not have an effective therapy for disease and its cause remains unknown. For several decades, research has focused on amyloidogenesis as the primary cause of disease. However, clearly satisfactory results have not been obtained in this line of research. In recent years there has been growing evidence about the role of neuroinflammation in AD and other neurodegenerative diseases. The role of ß-Amyloid as an element of the innate immune response places it in a new position in the pathophysiology of the disease. Alterations of intestinal and oral microbiota could have a role in the generation of neuroinflammatory changes, either directly by pathogens or by bacterial endotoxins. Endotoxins are polysaccharides of gram-negative bacteria that produce a potent immune reaction. Recently, there is evidence that gingipains have a role in production of neurotoxicity and amyloidogenesis. Gingipains are endotoxins produced by a pathogen associated with chronic periodontitis, Porphyromonas gingivalis. Gingipains generate direct neurotoxicity and its effect could be reversed with various molecules that are currently under development.