Our proposed multidisciplinary approach to aging includes the continued study of the degree of aneuploidy exhibited by first-degree asymptomatic relatives of our familial Alzheimer patients. This genetic marker may help us identify at-risk patients. We also wish to further characterize tubulin in synaptic subfractions and study how normal tissues and tissues from Alzheimer patients dispose of silicon. We plan to study the effects of antioxidants, and antioxidative enzymes on 1) clinical and biochemical parameters in the canine form of Batten's disease, and 2) their effect on life span and lipofuscin deposition in Drosophila. The free radical content of lipopigments from Batten's disease and for tissues at various ages throughout the life span of dogs and Drosophila will also be studied. We will characterize unsaturated lipids and lipid hydroperoxides levels in Batten's disease and throughout aging. Studies to isolate and characterize the deficient isoperoxidase in Batten's disease, and to record changes during aging of all of the peroxidase isoenzymes will be initiated. Lewy bodies will be isolated and studied to further characterize their chemical composition using infra-red spectrophotometry, gas chromatography - mass spectroscopy, and high pressure liquid chromatography. We plan to precisely localize the decrease of norepinephrine, dopamine and cyclic AMP in various nuclear groups of the rat brain, and to clarify the recovery process by which rats readjust to unilateral lesions of the locus coeruleus.