Recent epidemiological studies have supported the correlation between Helicobacter pylori infection and the development of Alzheimer's disease. HpHpn, a histidine-rich H. pylori protein, forms amyloid-like oligomers; it may be a pathogenic factor for Alzheimer's disease progression. HpHpn may also be transported from the gastric epithelium to the brain. However, HpHpn is secreted from H. pylori on the outer surface of gastric epithelia; therefore, the hypothesized movement of HpHpn across the gastric epithelium to the blood remains controversial. Here, we found the HpHpn showed acidic pH-dependent cellular uptake and subsequent secretion in human gastric epithelial-like carcinoma cells. Furthermore, HpHpn exhibited in vitro permeability across the blood-brain barrier. Although further in vivo experiments are required, our findings suggest that in vitro transcytosis of HpHpn in gastric epithelial cells and the blood-brain barrier may provide new insights into the correlation between H. pylori infections and Alzheimer's disease progression.
Keywords: Helicobacter pylori; blood–brain barrier; cell penetration; histidine-rich protein; transcytosis.
© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.