Individual dopaminergic neurons show raised iron levels in Parkinson disease.
OBJECTIVE
Evidence suggests that abnormal iron metabolism is associated with Parkinson disease (PD), with raised iron levels found in pathologically affected areas in PD. It is unknown if this elevated iron is actually associated with neurons or reactive glia, and we therefore addressed this issue by determining if raised iron was present in single dopaminergic neurons.


METHODS
We used unfixed frozen sections from postmortem tissue of PD patients and elderly normal individuals to avoid metal contamination and translocation. Levels of iron and other elements were measured using sensitive and specific wavelength dispersive electron probe x-ray microanalysis coupled with cathodoluminescence spectroscopy in individual substantia nigra dopaminergic neurons.


RESULTS
We identified raised intraneuronal iron in single defined substantia nigra neurons in PD (mean neuronal iron 2,838 vs 1,611, p < 0.0001) but not in other movement disorders such as Huntington disease. These findings were unrelated to the density of remaining neurons.


CONCLUSIONS
Primary changes in neuronal iron could lead to neurodegeneration in Parkinson disease.
Oakley
A E
AE
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Collingwood
J F
JF
Dobson
J
J
Love
G
G
Perrott
H R
HR
Edwardson
J A
JA
Elstner
M
M
Morris
C M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D004577:Electron Probe Microanalysis / Q000379:methods; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019581:Neuropil / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D013057:Spectrum Analysis / Q000379:methods; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation
D015415:Biomarkers; D005293:Ferritins; D007501:Iron; D004298:Dopamine