Sequestration of iron by Lewy bodies in Parkinson's disease

Central to the oxidative stress hypothesis of Parkinson's disease (PD) path ogenesis is the ability of iron to generate hydroxyl radicals via the Fento n reaction, and the consistent demonstration of iron elevation in the pars compacta region of the substantia nigra. However, uncertainty exists as to whether the excess iron exists in a state suitable for redox chemistry. Her e, using a method we developed that detects redox-active iron in situ, we w ere able to demonstrate strong labeling of Lewy bodies in substantia nigra pars compacta neurons in PD. In contrast, cortical Lewy bodies in cases of Lewy body variant of Alzheimer's disease were unstained. While the presence of elevated iron in PD substantiates the oxidative stress hypothesis, one must remember that these are viable neurons, indicating that Lewy bodies ma y act to sequester iron in PD brains in a protective, rather than degenerat ive, mechanism. The absence of redox-active iron in neocortical Lewy bodies highlights a fundamental difference between cortical and brain stem Lewy b odies.