son Study Group, 1993). Follow-up publications reported again that α-tocopherol had no benefit (Shoulson, 1998) and had no effect on mortality (Parkinson Study Group, 1998). This did not appear to be a result of poor compliance because increases in vitamin E in cerebrospinal fluid in response to the supplement were reported (Vatassery et al., 1998).

Alzheimer's Disease and Down's Syndrome. Alzheimer's disease is a neurodegenerative disorder that appears to have an oxidative stress component; it is not clear if this is a cause or a consequence of the disease. The disease may be potentiated by an accumulation of redox-active metals (Cornett et al., 1998), especially iron (Smith et al., 1997). Additionally, amyloid β-peptide is a key factor in the neurotoxicity of Alzheimer's disease because it can initiate protein oxidation and lipid peroxidation (Keller et al., 1997), eventually leading to neuronal cell death. The free-radical dependence of β-amyloid-associated toxicity was confirmed by the ability of vitamin E to prevent the toxic effects of amyloid β-peptide in vitro (Subramaniam et al., 1998). These data are compatible with an etiology that includes oxidative damage, but other hypotheses are possible.

In a 2-year, double-blind, placebo-controlled, randomized, multi-center trial in 341 patients with moderately severe impairment from Alzheimer 's disease, treatment with all rac-α-tocopherol (2,000 IU/day) significantly slowed the progression of disease (Sano et al., 1997).

A case can be made for a link between oxidative stress and neuropathology in Alzheimer's disease and Down's syndrome (Muller, 1994). In individuals dying from either disease, abnormalities in brain histology are remarkably similar. Down's syndrome is due to trisomy of chromosome 21, which carries the gene for superoxide dismutase (SOD). Interestingly, overexpression of human SOD in transgenic mice is associated with increased lipid peroxidation in the brain (Ceballos-Picot et al., 1991), perhaps secondary to SOD-induced conversion of the superoxide anion to hydrogen peroxide and water. Although these results are promising, it is still too early to draw any conclusions about the usefulness of vitamin E in Alzheimer's disease and Down's syndrome.

Tardive Dyskinesia (TD). TD is a neurologic disorder that develops in about 20 percent of patients treated long term with neuroleptic drugs. These drugs increase the turnover of brain catecholamines, particularly the neurotransmitter dopamine, and these are compounds that can give rise to ROS. TD is characterized by a



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