Develop Screening Assays to Differentiate ApoE Isoforms

Carl Frieden, PhD Washington University


The primary cause for developing late-onset Alzheimer's disease rests in the properties of one of the ApoE isoforms, specifically a variant called “apoE4.” The screening procedures developed in Dr. Carl Frieden’s experiments are designed to lead to the long term goal of finding therapeutic agents that specifically target ApoE4 without disrupting the physiological function of the “normal” ApoE3, a variant that does not increase risk for Alzheimer’s disease. The hypothesis is that such agents will alter the deleterious effects of ApoE4 and thereby delay or prevent the onset of Alzheimer's disease.

Project Details

The protein ApoE3 is essential for lipid and cholesterol metabolism. An almost identical protein, present in more than 5% of the population, is ApoE4.  This variant is a major risk factor for developing Alzheimer's disease. The long-term objective of this study is to find ways to disrupt the behavior of ApoE4 without disrupting that of ApoE3. To do this Dr. Carl Frieden and his team will start by developing screening procedures that can be used to develop therapeutic agents that specifically target ApoE4. If successful, the next step will be to start high throughput screening procedures to develop agents that utilize the screening methods the scientists develop. The team includes individuals who are experts in computational docking approaches and organic chemists who can modify potential therapeutic agents defined by screening libraries and computational approaches.