OXIDATIVE STRESS DURING THE PATHOGENESIS OF ALZHEIMERS-DISEASE AND ANTIOXIDANT NEUROPROTECTION

Alzheimer's disease (AD) is one of the most frequent causes of dementi a in the aged. The elucidation of the pathomechanisms of this neurodeg enerative disease with age, as the only risk factor for the majority o f cases, is in the centre of the efforts of molecular and cellular neu robiology in preclinical research. Various findings point to the invol vement of the amyloid beta protein (A beta) in the pathogenesis and pr ogression of AD. Precipitated A beta aggregates are found in the brain of AD patients post mortem in the so-called plaques, a major histopat hological hallmark of this progressive destructive disease. A beta can be toxic to cultivated neuronal cells only in its aggregated fibril f orm. After interaction with the neuronal cell membrane, these aggregat es can induce intracellular oxidative events and can lead to the relea se of so-called free radicals. This is just one important finding for the involvement of oxidative events in the nerve cell degeneration in AD supporting the oxidative stress hypothesis. Furthermore, different neurochemical methods revealed many additional traits and scars of oxi dative reactions in the brain of AD patients. Inflammatory events also seem to take part in the generation of an oxidative environment and t herefore in nerve cell death as well. In addition, various age-depende nt pathophysiological changes can increase neuronal vulnerability. Dif ferent antioxidants can protect cultivated neurons against A beta toxi city, but also against other oxidative stressors relevant to the disea se. Besides the classical lipophilic antioxidant vitamin E, the female sex hormone oestrogen could also play an important neuroprotective ro le as an antioxidant, as was shown recently. Oestrogen, oestrogen deri vatives, but also other potential free radical scavengers could block the accumulation of oxidative events on the long run and could, theref ore, possibly slow down or prevent progressive nerve cell death of AD, which occurs over decades. If future clinical trials using antioxidan ts as neuroprotectants in AD would also support the oxidative stress h ypothesis of the aetiopathogenesis of AD, antioxidants identified in t he laboratory could then find their way more and more into the clinica l treatment of Alzheimer's dementia.