Alzheimer's disease (AD) is the most common cause of dementia in older people. It is estimated that about 4 million individuals in the United States have AD, and as many as 350,000 individuals develop AD each year. AD is second only to cancer as the most expensive disease in the US with estimated expenditures of $100 billion per year including both direct and indirect medical cost.  Currently, there are no effective therapeutic strategies for disease prevention and long-term treatment.

Recent evidence has implicated oxidative damage as the earliest event in the progression of AD and suggests that it plays a key role in neuronal cell death in AD patients. Neuroprotective/antioxidative compounds could be a promising approach to slow disease progression and limit the extent of neuronal cell loss in AD.

AD AND OXIDATIVE STRESS/DAMAGE
A hallmark of AD is a marked increase in the evidence of oxidative damage in the neurons of AD patients, and a large body of recent work has identified increases in the signs of oxidative stress and resultant damage in the neuronal tissue of AD patients. Much of this damage has been identified in both amyloid plaques and neurofibrillary tangles, which have been shown to act as molecular sinks for redox-active Fe and Cu atoms. Additionally, a number of lines of evidence now indicate that oxidative damage and anti-oxidative stress responses precede clinical manifestation of the disease, and may be a major predisposing factor for the development of AD. Consequently, oxidative stress, and the events and conditions that generate it, are prime targets for therapeutic intervention in AD.

NEUROPROTECTION
Neuordegeneration as seen in AD is likely a function of the same signaling cascade that is active in ischemic stroke. In fact, one arm of this cascade leads directly to the production of free radicals that are key mediators of oxidative stress and damage. As such, drugs designed to regulate and/or reverse this signaling cascade are likely to be of great benefit for neuronal protection and preservation of brain function in AD, and perhaps in many other neurodegenerative diseases as well.