Helicobacter pylori infection contributes to the expression of Alzheimer's disease-associated risk factors and neuroinflammation

Maryam Noori; Ramina Mahboobi; Ali Nabavi-Rad; Shaghayegh Jamshidizadeh; Farzaneh Fakharian; Abbas Yadegar; Mohammad Reza Zali

doi:10.1016/j.heliyon.2023.e19607

Helicobacter pylori infection contributes to the expression of Alzheimer's disease-associated risk factors and neuroinflammation

Heliyon. 2023 Aug 29;9(9):e19607. doi: 10.1016/j.heliyon.2023.e19607. eCollection 2023 Sep.

Authors

Maryam Noori¹, Ramina Mahboobi², Ali Nabavi-Rad¹, Shaghayegh Jamshidizadeh¹, Farzaneh Fakharian¹, Abbas Yadegar¹, Mohammad Reza Zali³

Affiliations

¹ Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Over time, mounting evidence has demonstrated extra-gastric manifestations of Helicobacter pylori infection. As such, a number of studies demonstrated the potential contribution of H. pylori infection to the incidence and progression of Alzheimer's disease (AD). Considering unanswered questions regarding the effect of H. pylori infection on brain activity, we sought to investigate the impact of H. pylori infection on the expression of AD-associated risk factors. We used two H. pylori clinical strains obtained from two patients with peptic ulcer and evaluated their influence on the expression level of AD-associated genes (APP, ApoE2, ApoE4, ABCA7, BIN1, Clu, CD33) and genes for inflammatory markers (TLR-4, IL-8, TNF-α) by RT-qPCR in human glioblastoma (U87MG) and astrocyte (1321N1) cell lines. The expression of inflammatory cytokines was further assessed by ELISA assay. The exposure of U97MG and 1321N1 cells to H. pylori strains resulted in a significant enhancement in the expression level of the risk allele ApoE4, while reducing the expression of the protective allele ApoE2. H. pylori infection remarkably increased the expression level of main AD-associated risk genes, and also pro-inflammatory cytokines. Furthermore, we noticed a substantial elevation in the mRNA expression level of transmembrane receptor TLR-4 following H. pylori infection. Our findings presented the potential for H. pylori to stimulate the expression of AD-associated risk genes and trigger neuroinflammation in the brain tissue. This, in principle, leads to the recommendation that AD patients should perhaps test for H. pylori infection and receive treatments upon positive detection.

Keywords: Alzheimer's disease; Apolipoprotein; Helicobacter pylori; Neuroinflammation; TLR-4.