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Casein Kinase Delta 1 Inhibitor Recovers Cognitive Deficits in APPPS1 Model of Alzheimer
Casein Kinase Delta 1 Inhibitor Recovers Cognitive Deficits in APPPS1 Model of Alzheimer's Disease
Submitted on 08 Mar 2018

A. Portugues, M.S., S. Nagaraj, A.Yunus, B.S., J.J. Gamsby, Ph.D., D. Gulick, Ph.D.
University of South Florida
This poster was presented at USF Health Research Day 2018
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Poster Abstract
Alzheimer's Disease (AD) is a neurodegenerative disease categorized by dementia and memory loss due to molecular changes, such as Beta-Amyloid accumulation. Alterations in the circadian rhythm, or the body's internal clock, can contribute to cognitive deficits in populations such as shift workers and patients with AD. Patients with AD tend to have symptoms of sundowning, which is often associated with a circadian rhythm disruption. We sought to target a key regulator of the clock, Casein Kinase 1 ε/δ (CK1ε/δ) by using a CK1ε/δ inhibitor, PF-670462, to improve circadian rhythmicity and cognitive performance. In this study, we used an APPPS1 mouse model of beta-amyloid plaque accumulation as a model of Alzheimer's Disease. Mice of ages varying between 3 and 14 months underwent daily injections of the drug at two doses, 10 mg/kg, which targets the δ isoform, and 30 mg/kg, which inhibits both isoforms of CK1. During treatment, behavioral tests including Fear Conditioning (FC), Forced Swim Test (FST), and Y-Maze were conducted to test learning and memory. Other tests included Open Field (OF), Social Interaction (SI), and Elevated Plus Maze (EPM) to determine differences in anxiety and depression. We saw recovery of memory and reduced anxiety in mice treated with PF-670462 and thus propose drugs targeting the circadian clock in an APPPS1 model of AD. We conclude that correcting circadian dysfunction with PF-670462 treatments leads to reduced anxiety in the APPPS1 model of Alzheimer's Disease. PF-670462 treatments also improve learning and memory in this model of AD, thus recovering the cognitive deficits associated with Alzheimer's Disease. Report abuse »
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