Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study.

Purpose: Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD. Methods: The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants. Results: IVW results showed that genus Anaerotruncus (P = 5.00 × 10-3), genus Candidatus Soleaferrea (P = 1.83 × 10-2), and genus unknown id.2071 (P = 3.12 × 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P = 3.17 × 10-2), genus Faecalibacterium (P = 2.67 × 10-2), and genus Ruminococcaceae UCG-011 (P = 4.04 × 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P > 0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P > 0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD. Conclusions: We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.

Relationship of Apolipoprotein E with Alzheimer's Disease and Other Neurological Disorders: An Updated Review.

Alzheimer's disease (AD) and other neurodegenerative diseases, for which there is no effective cure, cause great social burden. Apolipoprotein E (APOE) is an important lipid transporter, which has been shown to have a close relationship with AD and other neurological disorders in an increasing number of studies, suggesting its potential as a therapeutic target. In this review, we summarize the recent advances in clinical and basic research on the role of APOE in the pathogenesis of multiple neurological diseases, with an emphasis on the new associations between APOE and AD, and between APOE and depression. The progress of APOE research in Parkinson's disease (PD) and some other neurological diseases is briefly discussed.