APOE Epsilon 4 Knock-In Rat Model of Alzheimer’s Disease

The etiology of Alzheimer’s disease (AD) is unknown but considered to be the combination of genetic and environmental factors together with aging. The most prevalent genetic risk for sporadic Alzheimer’s disease is the allele Ɛ4 of the apolipoprotein E4 (APOE Ɛ4). The many neuropathological findings that define AD are associated with APOE Ɛ4 carriers together with general cerebrovascular impairment and neuroinflammation. There are reports from human imaging studies that suggest the apoE4 protein could affect neurodevelopment many years before the onset of AD. Indeed, brain structure alterations may precede overt cognitive impairment in AD by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. In collaboration with Horizon Discovery (St Louis) we characterized the brain and cognitive development of male and female APOE Ɛ4 knock-in (KI) rats, a preclinical model of Alzheimer’s disease.