The roles of helicobacter pylori infection on the pathogenesis of Alzheimer's disease: Gut-brain axis dysfunction and blood-brain barrier disruption.

AD patients with HP infection exhibited impaired overall cognition and specific cognitive domains compared to AD patients without HP infection.

• 62 total AD patients were categorized into AD with HP (AD-HP) and AD with no HP (AD-nHP) groups
• HP infection was confirmed by 13C-urea breath test
• Impaired cognitive domains included immediate and short-term memory and language
• Overall cognitive score was positively correlated with amyloid-β42 and negatively with P-tau181 levels in CSF

AD patients with HP infection had elevated CSF levels of blood-brain barrier disruption markers MMP9 and VEGF.

• Matrix metallopeptidase (MMP) 9 levels were elevated in CSF of the AD-HP group
• Vascular endothelial growth factor (VEGF) levels were elevated in CSF of the AD-HP group
• P-tau231 was positively correlated with BBB variables including receptor for advanced glycation endproducts (RAGE), MMP9, zonula occludens-1, and claudin-5
• HP was particularly associated with elevated CSF VEGF level (p < 0.05)

AD patients with HP infection showed elevated CSF levels of neuroinflammatory markers interferon-γ and soluble TREM2.

• Interferon-γ levels were elevated in CSF of the AD-HP group
• Positive correlations were observed between P-tau181 and soluble triggering receptor expressed on myeloid cells 2 (sTREM2)
• Positive correlations were observed between P-tau231 and chitinase-3-like protein
• BBB variables, neuroinflammatory factors, and AD biomarkers were measured in cerebrospinal fluid using enzyme-linked immunosorbent assay

AD patients with HP infection demonstrated a unique dysbiosis pattern of gut microbiota and metabolites.

• Gut microbiota was profiled by 16S ribosomal RNA gene sequencing
• Gut metabolites were profiled by gas chromatography-mass spectrometry
• HP was particularly associated with reduced gut 23-nordeoxycholic acid methyl ester (p < 0.05)
• Correlations and linear regression among gut microbiota, metabolites, BBB variables, neuroinflammatory factors, and AD biomarkers were analyzed

AD patients with HP infection had elevated CSF levels of phosphorylated tau (P-tau) 181, indicating accelerated AD pathology.

• P-tau181 was elevated in the AD-HP group CSF
• Overall cognitive score was negatively correlated with P-tau181 levels in CSF
• P-tau181 was positively correlated with sTREM2
• P-tau231 was positively correlated with BBB variables including RAGE, MMP9, zonula occludens-1, and claudin-5