The question of the temporal association between increased iron and neurodegeneration in PD is unclear. Earlier authors suggested that the increase in iron might be a late or secondary event in the disease process; Dexter et al.  reported unchanged nigral iron levels in cases of so-called incidental Lewy body disease, representing an early preclinical state of PD. Their conclusion that increased iron only occurs in advanced stages of neurodegeneration was supported by unchanged SN iron concentrations in 'mild' PD cases, assessed semi-quantitatively as a mild nigral neuronal loss . However, more recent work using transcranial ultrasound indicates that increased iron can be demonstrated in the SN in PD patients even prior to the onset of clinical symptoms , suggesting that iron increase might occur earlier than previously thought.
While both the sources and timing of increased iron in PD SN are still controversial, its presence appears to be involved in the two primary pathogenic pathways associated with neurodegenerative changes in PD, oxidative stress and Lewy body formation.
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