ROS effects on neurodegeneration in Alzheimer's disease and related disorders: on environmental stresses of ionizing radiation.

Neurodegenerative processes associated with Alzheimer's disease are complex and involve many CNS tissue types, structures and biochemical processes. Factors believed involved in these processes are generation of Reactive Oxygen Species (ROS), associated inflammatory responses, and the bio-molecular and genetic damage they produce. Since oxidative processes are essential to energy production, and to other biological functions, such as cell signaling, the process is not one of risk exposure, as for cigarettes and cancer, but one where normal physiological processes operate out of normal ranges and without adequate control. Thus, it is necessary to study the ambiphilicity that allows the same molecule (e.g., beta amyloid) to behave in contradictory ways depending upon the physiological microenvironment. To determine ways to study this in human populations we review evidence on the effects of an exogenous generator of ROS, ionizing radiation, in major population events with radionuclides (e.g., Hiroshima and Nagasaki; Chernobyl Reactor accident; environmental contamination in Chelyabinsk (South Urals) where plutonium was produced, and in the nuclear weapons test area in Semipalatinsk, Kazakhstan). The age evolution, and traits, of neurodegenerative processes in human populations in these areas, may help us understand how IR affects the CNS. After reviewing human population evidence, we propose a model of neurodegeneration based upon the complexity of CNS functions.