Sequestration of iron by Lewy bodies in Parkinson's disease.
Central to the oxidative stress hypothesis of Parkinson's disease (PD) pathogenesis is the ability of iron to generate hydroxyl radicals via the Fenton 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. Here, using a method we developed that detects redox-active iron in situ, we were 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 may act to sequester iron in PD brains in a protective, rather than degenerative, mechanism. The absence of redox-active iron in neocortical Lewy bodies highlights a fundamental difference between cortical and brain stem Lewy bodies.
Castellani
R J
RJ
Institute of Pathology, Case Western Reserve University, Cleveland OH 44106, USA.
Siedlak
S L
SL
Perry
G
G
Smith
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D016631:Lewy Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D014018:Tissue Distribution
D005290:Ferric Compounds; D005296:Ferrous Compounds; D007501:Iron