The research of the Cotman laboratory is aimed toward understanding the mechanisms causing neuronal degeneration in Alzheimer’s disease (AD) and the development of interventions to promote successful aging. We have been investigating the possibility that the accumulation of risk factors in the aged brain such as beta-amyloid and oxidative damage activate pathways associated with apoptosis. As predicted from cell culture models, caspases and related pathways are up regulated and caspase cleavage products of proteins such fodrin; APP and tau accumulate in the AD brain. In the case of fodrin the accumulation parallels that of tangle formation, suggesting that like tangles this mechanism correlates with cognitive decline (Rohn, 2000).