cAMP Response Element Binding Protein (CREB) as a Marker of Cognitive Function in Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive dysfunction and memory impairments. The cause of these impairments is unknown. Cyclic-AMP Response Element Binding Protein (CREB) signaling is known to be critical for the formation of long-term memory. This thesis demonstrates that CREB signaling is impaired in the APPswe/PS1ΔE9 mouse model of familial AD, and that these deficits correspond to impaired performance on learning and memory tasks. Importantly, these deficits were observed in young adult mice prior to the onset of advanced pathology. This observation suggests that dysfunctional CREB signaling may not be tied to the progression of the pathological hallmarks of Alzheimer’s disease, which are poorly correlated with cognitive dysfunction and disease progression. Importantly, this thesis also demonstrates that activated CREB is diminished in the peripheral blood mononuclear cells of persons with AD, and that expression of activated CREB in the blood during life correlates to the expression of activated CREB in the postmortem brain in persons with AD. Therefore, expression of CREB signaling components in the blood may reflect CREB signaling in the brain, and by extension, cognitive function. This thesis proposes that CREB signaling factors may serve as biomarkers of cognitive function in Alzheimer’s disease.