2005 Investigator-Initiated Research Grant

Alzheimer researchers often study the disease with the aid of animal models, usually mice that are genetically altered to develop certain features of the disease. Current studies with Alzheimer animal models have greatly advanced our understanding of the abnormal changes that occur in brains of individuals with the disease.

Alzheimer’s involves a number of complex factors, including the beta-amyloid protein fragment and immune-system components that induce inflammation. In order to evaluate the significance and interrelationship of these factors, as well as the potential for improvement if one or more of the factors can be modified, it would be useful to have an animal model in which these factors can be controlled.

Richard Flavell, Ph.D., F.R.S., and colleagues are developing a new line of mice carrying a human gene that results in the production of beta-amyloid. This gene will be engineered in such a way that researchers can “turn it off” by feeding mice a certain antibiotic. The researchers will assess how well this mouse model reflects the pathology of Alzheimer’s disease and will observe the impact of stopping beta-amyloid production.

These mice will also be crossed with another line of mice lacking important immune-system molecules that cause inflammation. Studies of the subsequent line of mice may clarify the link between beta-amyloid accumulation in the brain and inflammation. The outcome of this investigation may help scientists more accurately characterize disease processes and identify targets for new drug therapies.