Alzheimer’s disease (AD) is the most common form of dementia. Its strongest genetic risk factor is the e4 allele of the apolipoprotein E (APOE), and risk scales with APOE-e4 load (e4/e4 > e4/e3 > e3/e3). APOE-e4 has been linked to distinct gut microbiome composition in murine models, but genotype effects on the human gut microbiome remain unclear. Here, we hypothesized differential gut microbiome composition in healthy, younger adults (20-35 years) with genetic AD risk (i.e., individuals carrying one copy of the APOE-e4 allele, APOE-e4/e3) compared to controls (i.e., APOE-e3/e3). We genotyped 574 individuals (APOE-e4/e3: 111/19%, 89 females, mean age=23 years; APOE-e3/e3: 381/66%, 250 females, mean age=23 years) and analyzed gut microbiome composition from stool samples (16S rRNA). Initial results showed increased alpha-diversity (diversity within samples) in the APOE-e4/e3 risk group compared to APOE-e3/e3 controls (observed ASVs, p=0.02; Shannon, p=0.016; Chao1, p=0.037). Analyses are currently ongoing and results regarding beta-diversity and differential abundance between groups will be presented at the meeting. Together, these findings are the first to show differences in gut microbiome composition in healthy, younger individuals with and without genetic AD risk. This highlights the gut-brain axis as a powerful target to ameliorate the potentially detrimental effects of APOE-e4 across the lifespan.