Gingipain Causes Tau Tangle Formation in Alzheimer’s Disease Brains via Regulation of TREM-1

Abstract

: Tau phosphorylation is widely believed as an indicator of Alzheimer’s Disease (AD). Recent evidence suggests that the periodontal pathogen, Porphyromonas gingivalis, is associated with AD development by increasing the level of tau protein in the brain. Gingipain, the major virulence factor of the bacteria, has been described to be involved in the cleavage of the Triggering Receptor Expressed on Myeloid cells 1 (TREM-1). The soluble TREM-1 (sTREM-1) generated was shown to result in the activation of tau phosphorylation. This work aims to uncover the underlying mechanism by which P. gingivalis causes AD by studying the relationship between the level of gingipain, TREM-1 and tau in the brain of mice infected with P. gingivalis. Through this study, a novel mechanism of AD formation may be proposed and can be exploited to generate therapies against the disease.