Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder that begins with memory loss and can lead to death. In Puerto Rico, AD is the fourth leading cause of death, while in the United States, it ranks fifth. Research suggests the gut microbiome contributes to the pathophysiology of AD by promoting inflammation and amyloid buildup in the brain. This study examined the composition and diversity of the gut microbiota in Puerto Ricans with AD compared to controls and its relationship with cognitive impairment severity and APOE status. We recruited 100 participants (50 AD, 50 controls), who underwent clinical and cognitive assessments (MoCA/CDR). While overall microbial diversity and richness showed no significant differences, specific bacterial taxa exhibited subtle differential abundance. Faecalibacterium and Bacteroides were moderately significant and increased on controls compared to AD. Moreover, individuals carrying the APOE E4 allele exhibited lower abundances of butyrate-producing bacteria and an enrichment of potentially pro-inflammatory genera, including Eggerthella and Lachnoclostridium. These findings suggest that gut microbiota dysbiosis may contribute to cognitive decline and AD progression, highlighting the potential for microbiome-targeted therapeutic interventions in AD prevention and treatment.