UC San Diego

Alzheimer’s disease (AD) is a debilitating form of dementia associated with cognitive disabilities. The underlying mechanisms that cause AD are still relatively unknown but stress and corticotropin releasing factor (CRF) has been shown to contribute to disease progression. CRF receptors have become a target for therapeutic potential in AD as it is part of the stress-signaling pathway. CRF antagonist (R121919) has shown to decrease amyloid beta plaques in animals early in AD development. Since R121919 is most affective in early stage disease development, we tested if this antagonist could produce the same results in transgenic AD mice (PSAPP) that were in late stage disease progression and when chronically stressed. We observed that R121919 is most affective in decreasing AD pathology and phenotypic changes in early stage AD mice when stressed; AD pathology was diminished in late stage AD progression as well. These findings indicated that drug administration with CRF antagonist slows down AD progression when stress is present in early stage AD development and has the potential to do the same in late stage AD progression. Our data demonstrate that CRFR1 receptors are a potential preventative therapeutic target for AD and that targeting them may be particularly beneficial for individuals who are prone to experiencing traumatic event.