Characterization of the 5xFAD Transgenic Mouse and the Effectiveness of Hydroxylpyclen in the Disaggregation of AB Plaques and Restoration of Cognitive Function in Alzheimer's Disease

Abstract

Alzheimer's disease (AD), a neurodegenerative disorder with no known cure or treatment, is the most prevalent form of age-related dementia. As both the rate and total number of those diagnosed continues to increase, AD has become a global concern. The transgenic 5xFAD mouse model expresses familial AD due to mutations in both amyloid-beta precursor protein (APP) and presenilin-1 (PS1). The AD hallmarks exhibited include amyloid-beta (A-beta) plaque deposition around 2 months of age and hippocampus synaptic dysfunction around 9 months of age, which result in severe accelerated cognitive impairment. Through contextual fear conditioning (CFC) and radial arm water maze paradigms, as well as Thioflavin-S A-beta plaque staining, this study characterized in our own lab the AD hallmarks that have been previously demonstrated in the 5xFAD mouse model. Copper-chelation, antioxidants, and reactive oxygen species (ROS) reduction have shown promise individually as potential treatment options for AD. The novel hydroxylpyclen from Green Research Laboratory has been previously shown to exhibit all of these capabilities, while not detrimentally interfering with cell processes or viability. Therefore, after characterization, this study explored hydroxylpyclen as a potential treatment in 9 month old, transgenic positive 5xFAD mice. By injecting mice daily for 28 days with 222mg/kg hydroxylpyclen, our lab has shown promise for an AD treatment option by producing improvement in context-dependent cognitive behavior as compared to controls in CFC, as well as reductions in A-beta hippocampal plaque and ROS species.