A QUANTITATIVE-ANALYSIS OF ISOFERRITINS IN SELECT REGIONS OF AGED, PARKINSONIAN, AND, ALZHEIMERS DISEASED BRAINS

The brain requires a ready supply of iron for normal neurological func tion, but free iron is toxic. Consequently, iron bioavailability must be stringently regulated. Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders suc h as Alzheimer's and Parkinson's diseases (AD and PD, respectively). A key component of the iron regulatory system in the brain is ferritin. Ferritin consists of 24 subunits, which are distinguished as either a heavy-chain (H) or light-chain (L) isoform. These peptide subunits ar e genetically and functionally distinct, Thus, the ability to investig ate separately the types of ferritin in brain should provide insight i nto iron management at both the cellular and the molecular level. In t his study, the ratio of isoferritins was determined in select regions of adult elderly AD and PD human brains. The H-rich ferritin was more abundant in the young brain, except in the globus pallidus where the r atio of H/L ferritin was 1:1. The balance of H/L isoferritins was infl uenced by age, brain region, and disease state. With normal aging, bot h H and L ferritin increased; however, the age-associated increase in isoferritins generally failed to occur in AD and PD brain tissue. The imbalance in H/L isoferritins was disease and region specific. For exa mple, in frontal cortex, there was a dramatic (fivefold) increase in t he ratio of H/L ferritin in AD brains but not in PD brains. In PD, cau date and putamen H/L ratios were higher than in AD and the elderly con trol group. The analysis of isoferritin expression in brain provides i nsight into regional iron regulation under normal conditions and sugge sts a loss of ability to maintain iron homeostasis in the two disease states. This latter observation provides further evidence of dysfuncti on of iron homeostatic mechanisms in AD and PD and may contribute sign ificantly to understanding the underlying pathogenesis of each, partic ularly in relation to iron-induced oxidative damage.