Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and loss of memory. Currently, 7 million Americans and millions more worldwide, aged 65 and older, are affected. Despite its prevalence, the underlying causes of AD are still debated, and much research concerning AD pathology is underway. There is a need for effective and efficient model organisms for studying the disease's common form, Sporadic AD (SAD). Zebrafish are a common and promising model for studying human disease, as they share similar brain and gastrointestinal structures to humans. Moreover, they possess app? and app?, which are co-orthologs of the human gene APP, associated with AD in humans. They can successfully be used to study AD and may provide an additional model for the gut-brain axis. Recent studies have highlighted the potential role of the gut microbiome in neurological diseases through this axis, with gut dysbiosis being hypothesized to lead to the onset and progression of AD. Zebrafish, however, have not yet been utilized to study the role of the gut-brain axis and its impact on AD. We hypothesize that gut dysbiosis contributes more significantly to the onset of AD. A chemical induction model using okadaic acid (OKA) for AD is attempted to be validated, with our results suggesting a viable threshold for OKA concentration and administration for successful induction of SAD in zebrafish. Our results indicate that antibiotic-induced gut dysbiosis may play a role in the onset of SAD, evidenced by a significant reduction in bacterial abundance and statistically significant upregulation of appa within brain tissue. This suggests that a healthy microbiota may assist in brain homeostatic protection, and that its disruption may leave affected individuals at risk for developing AD.
