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2005 Grant - LaFerla

Learning and Memory Deficits in a Mouse Model With Plaques and Tangles

Frank M. LaFerla, Ph.D.
University of California
Irvine, California

2005 Zenith Fellows Award

The pathological hallmarks of Alzheimer's disease are two kinds of abnormal structures in the brain: amyloid plaques, which form outside of cells and are composed primarily of the beta-amyloid protein fragment, and neurofibrillary tangles, which form inside cells and are composed of the altered tau protein. The exact link between these lesions or their components and the onset and progression of cognitive deficits is not clearly established.

Frank M. LaFerla, Ph.D., and his colleagues have developed a line of genetically altered mice that develop plaques and tangles in regions of the brain which are affected in humans with Alzheimer's disease, and the mice develop age-associated memory and learning impairments in a manner similar to the onset and progression of dementia symptoms.

The investigators will conduct memory and learning assessments with these mice to test the hypotheses (1) that very early accumulation of beta-amyloid inside cells alters cellular function, induces dysfunction in cell-to-cell communication systems, and results in certain memory impairment, (2) that later development of plaques and tangles causes structural changes in cells, prompting other kinds of impairments, (3) and that treatments will reverse these deficits in the mouse model. They will also correlate genetic information and pathological brain changes with deficits in specific cognitive skills. The findings from these studies may clarify the role of beta-amyloid in Alzheimer's disease and support efforts to develop disease-modifying drugs.