Gene expression in brain cells during Alzheimer' disease (AD) and aging will be studied to resolve changes in relation to likely causes that include transynaptic responses, interactions of steroids with neuronal degeneration, and glial reactivity. Two projects and 3 pilot grants are proposed by the PI and junior investigators in the research group (Drs. Patrick may, David Morgan and Nancy Nichols): 1. Analysis of mRNA changes during hippocampal and cortical neuron sprouting as response to damage afferents (C.E. Finch and P. May, PI) 2. Mechanisms of glial hyperactivity (D. Morgan, PI) Pilot Projects 1. Messenger RNA and Interventions into Neuronal Atrophy (S. Johnson and C.E. Finch PI) 2. Corticoids, Glutamine Synthase and Neurodegeneration (P. May and C.E. Finch, PI) 3. Stress-related Changes in Brain RNA of Vervet Monkeys (N. Nichols and C.E. Finch, PI) Comparisons will be made between changes in postmortem human brain and rodent models, in which we will test the manipulatability of the modelled lesions. These projects will also evaluate the long- standing but inadequately tested view that there are major impairments of RNA and protein synthesis during aging and AD. In addition, the findings bear on the selectivity in neurodegeneration during aging and AD: The apparently maintained functions of some neurons gives a basis for optimism that advancing age is not a sufficient cause of neurodegeneration, and that specific mechanisms may be found to prevent or reverse the degenerative changes. Members of this program will also train pre-and postdocs in experimental approaches to age-related neurodegeneration, and will give lectures to undergraduates in the pre-health sciences major of the Leonard Davis School of Gerontology.