James Cleary, PhD
University of Minnesota
Minneapolis, Minnesota

2003 Investigator-Initiated Research Grant

Plaques and tangles in the brain are the pathological hallmarks of Alzheimer’s disease. Plaques are accumulations of the abnormal protein fragment beta-amyloid, trimmed off its parent molecule amyloid precursor protein (APP). Tangles are abnormal aggregations of the protein tau. These two proteins are the prime suspects for memory decline and other cognitive problems in the disease, although scientists differ on the relative importance of each protein. Mice genetically engineered to have the human genes for APP or tau are among the most useful research tools that might help resolve this question.

James Cleary, PhD, and colleagues are studying one of the newest genetically engineered models of Alzheimer’s, a “double transgenic” mouse that, unlike most earlier models, produces both plaques and tangles. The researchers will examine how this combination affects memory and other cognitive abilities as the mice age. They will also test whether an antibody to beta-amyloid, called BAM-10, can reduce plaques and improve cognition. Previous research indicates that BAM-10 will probably reduce plaques, but Cleary and his colleagues believe that the presence of tau tangles in this transgenic mouse will eventually make cognitive defects irreversible. Data supporting this hypothesis may suggest that there is a critical time in the progression of Alzheimer pathology when treatment may be most effective.