Possible use of adaptation to hypoxia in Alzheimer's disease: A hypothesis

Disorders in memory and other cognitive functions in Alzheimer's disease (AD) may result from an exhaustion of adaptive reserves in the brain. Therefore it is a challenge to find methods to increase the adaptive reserve of the organism to combat AD. Excitotoxicity, Ca2+ homeostasis disruptions, oxidative stress, disturbed synthesis of NO, and impaired cerebral circulation are suggested as key pathogenic factors of AD. At present it appears that stimulation of the self-defense systems in neural cells is a promising strategy in restricting the progression of AD. These systems include those of antioxidants, heat shock proteins (HSPs), NO, and other so-called stress-limiting systems. Non-drug activation of these systems can be achieved most efficiently by adaptation of the organism to environmental challenges, such as hypoxia. In this paper the potential of methods used in adaptive medicine is explored. The protective mechanisms of adaptation to hypoxia may be related to restriction of oxidative stress in the hippocampus, the limitation of a decrease in NO production induced by β-amyloid, and increased density of the vascular network in the brain. In this review we selectively present data that support the idea that adaptation to hypoxia is a possible non-drug means in the prevention of AD. In our opinion this strategy may provide a break-through in the clinical approach of this disease. © Med Sci Monit, 2005.