Causal effect of serum lipopolysaccharide activity levels and inflammatory proteins on Alzheimer's disease: A Mendelian randomization study combined with meta-analysis in a large-scale cohort.
Level 3 - non-randomized controlled study
Two-sample Mendelian randomization study using observational summary-level genetic data
PubMed 41064738 · doi:10.1177/25424823251385589
What was done
A two-sample Mendelian randomization (MR) study combined with meta-analysis was performed to evaluate the causal effects of serum lipopolysaccharide (LPS) activity levels and 91 inflammatory proteins on Alzheimer's disease (AD). The analysis included genetic data from cohorts comprising 1,260,136 sporadic AD and 2,838,825 familial AD individuals across multiple independent datasets.
What was found
Genetically predicted serum LPS activity level was associated with increased risk of early-onset sporadic AD (OR = 1.392, 95% CI: 1.038–1.869). However, meta-analysis across 10 independent datasets found no overall association between LPS and sporadic AD. Meta-analysis across 8 familial AD datasets also showed no significant association. AXIN1 and IL-1 alpha were identified as significant risk factors for sporadic AD, though specific effect sizes and confidence intervals were not reported in the abstract.
Why it matters
This study provides evidence on whether circulating bacterial endotoxin and specific inflammatory markers play a causal role in Alzheimer's disease subtypes, finding a signal confined to early-onset sporadic cases rather than broader AD cohorts.
Limits
Overall meta-analyses for sporadic and familial AD were null. Numerical estimates, odds ratios, and confidence intervals for the inflammatory proteins (AXIN1, IL-1 alpha) were not reported in the abstract. MR estimates are vulnerable to horizontal pleiotropy and population stratification.
Cited by
- supports Elevated circulating levels of lipopolysaccharide (LPS) and anti-LPS antibodies correlate with Parkinson's disease, Alzheimer's disease, and multiple sclerosis.