The Effects of CRF1 Antagonism on Spatial Navigation and Long-Term Potentiation in the TgF344-AD Model of Alzheimer’s Disease

Alzheimer’s disease is characterized by neurobiological deterioration and cognitive impairment that is irreversible. Alzheimer’s disease patients exhibit increased stress system abnormalities including upregulation of the corticotropin releasing factor type 1 receptor (CRF1) and elevated levels of cortisol. People experiencing increased psychological distress in life are more likely to be diagnosed with Alzheimer’s disease and experience faster rates of neurocognitive decline. Therefore, the current dissertation aimed to examine the underlying systems involved in Alzheimer’s disease neuropathology and stress. Administration of the CRF1 antagonist, Antalarmin, reduces AD pathogenesis and anxiety-like behavior in models of Alzheimer’s disease. Thus, the current project used the TgF344-AD model to elucidate the mechanistic functions of CRF1 on the progression of AD neuropathology. Through examination of CRF1 antagonism, anxiety-like behavior, spatial navigation and memory, and alterations of long-term potentiation in the hippocampus, this project provides a comprehensive understanding of Alzheimer’s disease and characterization of TgF344-AD responding.