William C. Mobley, M.D., Ph.D.
Stanford University
Stanford, California

2005 Investigator-Initiated Research Grant

Alzheimer’s disease is characterized by functional and structural changes in brain cells. One group of brain cells, the basal forebrain cholinergic neurons, is of particular interest to Alzheimer researchers because of their role in learning, memory formation and attention. By learning more about the actions of these cells, it may be possible to better understand the cellular events that lead to dementia symptoms.

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. William C. Mobley, M.D., and colleagues are studying aspects of basal forebrain cholinergic neuron function in a mouse model of Down syndrome. They have selected this animal model because nearly all older people with Down syndrome exhibit the pathological features of Alzheimer’s.

In studies of basal forebrain cholinergic neurons from Down syndrome mice, the research group has documented a defect in the transport of nerve growth factor, a protein that promotes nerve cell growth and provides cells protection from damage. Additionally, they have identified amyloid precursor protein (APP), a protein highly implicated in Alzheimer’s disease pathology, as a possible cause of the nerve growth factor transport defect. They believe that a failure in nerve growth factor transport may occur in both Alzheimer’s disease and Down syndrome.

In this current study, the investigators will examine and characterize the mechanism of action by which APP may disrupt nerve growth factor transport. The outcome of this work may clarify key processes contributing to dementia and suggest new strategies for treating Alzheimer’s disease.