Aging and Alzheimer's Disease

James Conner, Associate Project Scientist
Alan Nagahara, Associate Project Scientist

The Aging and Alzheimer’s Disease Research Group in the Center for Neural Repair studies degenerative changes in the brain that are a consequence of both normal aging and pathological disorders such as Alzheimer’s disease. We explore the hypothesis that nervous system growth factors, including Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), and other trophic molecules influence neuronal survival and function at molecular, cellular, electrophysiological and behavioral levels.

These programs contribute to our understanding of mechanisms underlying neuronal vulnerability to degeneration, and represent translational programs for developing more effective therapies for neurodegenerative disorders. This work resulted in the first human clinical trial of gene therapy in an adult neurological disorder: in 2001, we initiated a program of NGF gene transfer to humans with Alzheimer’s disease. This work is continuing and moving through later stage clinical trials.

A related program is determining the potential of BDNF to prevent or reduce cell degeneration in important cortical regions of the brain. This program may also be translated to human clinical trials in the future.

At a more basic level, we are attempting to discover genes that correlate with risk to neurodegeneration as a function of normal aging, and how growth factors modify age-related changes in gene expression. We are further defining how normal aging influences neuronal structure at the level of dendritic spine density and morphology, and influences of growth factors on these degenerative changes.