Michael Agadjanyan, Ph.D., D.Sc.
Institute for Molecular Medicine
Huntington Beach, California

2003 Investigator-Initiated Research Grant

Scientists are evaluating different techniques for reducing brain levels of the protein fragment beta-amyloid, the prime suspect in Alzheimer’s disease. Several of these approaches take advantage the body’s natural systems for clearing beta-amyloid from the brain. One approach that has shown promise in animal models of the disease is a form of vaccination, where beta-amyloid injections induce the body to develop anti-beta-amyloid antibodies that boost its rate of beta-amyloid clearance. However, many researchers are concerned that the foreign beta-amyloid could have unwanted consequences, such as contributing to the death of brain cells or triggering harmful immune system responses. In fact, a recent human clinical trial of beta-amyloid vaccine was halted after some participants developed brain inflammation.

One appealing alternative is to find nontoxic molecules that will boost the clearance of beta-amyloid. Michael Agadjanyan, PhD, DSc, and colleagues have found several molecules that mimic beta-amyloid (termed “mimotopes”) in mice, and they are now looking for corresponding mimotopes in humans. In this study, they will use use blood from people with Alzheimer’s disease to find beta-amyloid mimotopes. They will then test these molecules in a mouse model of Alzheimer’s disease to determine whether vaccination with human mimotopes can reduce mouse brain levels of beta-amyloid and reverse memory deficits, without side effects.