Reduced allelic dosage of CLP1 attenuates cognitive dysfunction and pathological burden in transgenic mouse models of Alzheimer’s disease

Case Western Reserve University, Cleveland OH

Investigators

Abstract

Project Summary/Abstract Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly caused by complex interactions of genetic and environmental risk factors. An estimated 130 million people will develop AD by 2050, constituting an urgent clinical need for effective treatments and therapies to be developed. Prior therapies have focused on resolving pathological hallmarks, such as senile plaques (Ab) and neurofibrillary tangles (tau), but have failed to improve cognitive function in patients. The RNA kinase, CLP1, was recently found to be a genetic mediator AD. Additionally, high mRNA levels of CLP1 correlated with poor cognitive function in patients. Our preliminary histological analysis of brain samples from dementia patients and a mouse model of AD, with controls, found a shared, aberrant expression pattern of CLP1 protein with disease. Together, these findings lead us to hypothesize that CLP1 overexpression may contribute to AD pathogenesis and cognitive decline in AD. To test this idea, we will intercross mouse models of AD with Clp1 heterozygous mutant mice and assess disease pathology and cognitive decline during AD progression for amelioration.