PURPOSE: Alzheimer's disease (AD) and wet age-related macular degeneration (wAMD) are both prevalent degenerative diseases in the elderly population. However, whether AD is causally related to wAMD is unclear. A Mendelian randomization(MR) analysis was conducted to investigate the association between them. METHODS: Single nucleotide polymorphisms (SNPs) involved in this study were acquired from the IEU Open Genome-wide association study (GWAS) database. As for AD (ID: finn-b-G6_ALZHEIMER), there were 3899 cases and 214,893 controls. For wAMD (ID:finn-b-WET_AMD), it contained 2114 cases and 206,601 controls. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses and Steiger test. RESULTS: The occurrence of wAMD was associated with decreased risk of AD (IVW, OR was 0.82 at 95%, Confidence interval (CI) of 0.77-0.88, CONCLUSIONS: Our findings demonstrated a potentially protective effect of AD against the development of wAMD. It promotes further investigation of interaction between AD and wAMD.