Page 296 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Helicobacter pylori infection and Alzheimer’s disease

activities and overall life quality. AD’s clinical importance Utilizing genetic data, MR analysis provides compelling
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is highlighted by its high prevalence and the substantial evidence that the pathogenesis of AD may be directly
burden it places on affected individuals and their families. influenced by H. pylori infection. This methodology not
7,8
Understanding the potential risk factors for AD becomes only enriches our comprehension of the etiological role of
increasingly imperative for guiding early intervention and the infection in AD but also holds substantial promise for
therapeutic strategies as the world’s population ages. 9,10 informing future therapeutic interventions.
Current investigation on the correlation between AD and 2. Materials and methods
infection is increasingly highlighting H. pylori’s potential
role in AD’s development. 11,12 Meta-analysis findings reveal 2.1. Data source
that H. pylori infection raises AD risk, with an OR of 1.40 The data on H. pylori infection in this study is sourced
in these patients, indicating a correlation between the from the literature by Butler-Laporte et al. We examined
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two. In addition, co-infection with periodontal pathogens six antibodies related to H. pylori infection: Anti-H. pylori
further exacerbates this risk, as seen in studies where CagA, Catalase, GroEL, OMP, UREA, and VacA, which
specific pathogens interact synergistically with H. pylori to correspond to genome-wide association studies (GWAS)
influence AD incidence. Mechanistically, H. pylori can cause database IDs GCST90006911 through GCST90006916. The
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increased β-amyloid deposition in the brain by altering the study sample is composed of European ancestry people,
gut flora and causing chronic low-grade inflammation. with sample size details presented in Table 1. IVs for AD
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Through the oropharyngeal olfactory route, the bacteria’s were extracted from the Finngen database, comprising
metabolites can reach the central nervous system, promoting 11,755 AD cases and 441,978 European ancestry controls.
neurodegenerative processes. Moreover, the buildup of All AD cases adhered to the criteria set by the International
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β-amyloid plaques, which are closely linked to the pathological Classification of Diseases (ICD-10).
features of AD, may be facilitated by the chronic inflammatory
state linked to H. pylori infection. However, numerous 2.2. MR analysis
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studies have predominantly employed observational designs, To determine the correlation among H. pylori infection
which are inherently constrained by potential biases and and AD, we conducted GSMR and a two-sample MR
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confounding variables. In addition, variations in sample investigation. SNPs were analyzed as IVs. During the
selection may limit the result’s generalizability, as certain whole procedure, it is crucial to validate three important
populations could not fully reflect the larger population. hypotheses to ensure optimal outcome accuracy. The
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Furthermore, reliance on specific instrumental variables first step involves confirming that the chosen IVs exhibit a
(IVs) in prior analyses may undermine the validity of direct association with the H. pylori infection. Second, it is
causal inferences. It is imperative that these methodological essential to establish the IVs’ independence from potential
constraints are addressed to improve our comprehension of confounders impacting both exposure and outcome.
the intricate relationship between infection and AD. Finally, ensuring that the IVs affect AD solely through
their influence on the risk factor.
To elucidate the correlation between them, our study
employed Mendelian randomization (MR) analysis, which We primarily employed the IVW approach as our MR
employs genetic variations as key variables to deduce analysis strategy. To fully evaluate the possible association,
causal relationships. A significant advantage of MR is
its capacity to simulate the conditions of a randomized Table 1. Baseline characteristics for participants
controlled trial, thereby addressing the constraints of
observational studies. Weighted median estimation, Exposure/ Data source Phenotype Sample size*
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Outcome
inverse variance weighting (IVW), weighted mode, and
MR-Egger regression are examples of common two-sample Alzheimer’s The FinnGen Alzheimer’s 11,755/441,978
disease
consortium
disease
MR techniques. These approaches are used to improve Antibodies Butler-Laporte CagA 985
the findings’ reliability as well as robustness. Generalized against H. pylori et al. 21
summary data-based MR (GSMR) presents distinct Catalase 1558
advantages over traditional MR. By taking into account GroEL 2716
linkage disequilibrium (LD) among genetic variants, OMP 2640
GSMR improves analytical efficiency. Furthermore, UREA 2251
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it employs or heterogeneity in dependent instruments VacA 1571
(HEIDI) test to identify instrumental outliers and exclude Note: *Sample size shown as a total number for quantitative traits and
pleiotropic single-nucleotide polymorphisms (SNPs). cases/controls for binary traits.
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Volume 9 Issue 3 (2025) 288 doi: 10.36922/EJMO025140087