Technical Abstract: For nearly two decades, the amyloid-ß (beta) hypothesis has dominated the field of Alzheimer's disease (AD) research and massive efforts have focused on the role of amyloid-ß in the pathogenesis of the disease. However, it still remains unclear whether amyloid-ß is either necessary or sufficient for the development of AD or whether it is responsible for the neurodegeneration or behavioral and cognitive deficits associated with the disease. A number of research groups, including Robinson and Bishop, have begun to question the supremacy of the amyloid-ß hypothesis, and many are now considering amyloid-ß to be a protective consequence to an underlying disease mechanism. There is increasing evidence that amyloid-ß may function as a trap or sink by binding and neutralizing neurotoxic solutes. The recent suspension of phase II clinical trials of the amyloid-ß vaccine ties to our understanding of the function of amyloid-ß and has called into question the validity of the amyloid-ß vaccine, which is based on the assumption that the removal of amyloid-ß plaques would be a beneficial treatment for AD. Since sensitivity of the neuronal environment to insults increases with advancing age, it is very likely that the most important parameter in the development of AD involves mechanisms that are strongly associated with aging, such as oxidative stress. It is possible that individuals predisposed to AD represent an already declining system and amyloid-ß serves as a life preserver to neurons that are surrounded by a sea of oxidative stress.