Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions

Abstract

Oxidant-mediated damage is suspected to be involved in the pathogenesis of several neurodegenerative disorders . Iron promotes conversion of hydrogen peroxide to hydroxyl radical and, thus, may contribute to oxidant stress . We measured iron and its transport protein transferrin in caudate, putamen, globus pallidus, substantia nigra, and frontal cortex of subjects with Alzheimer's disease (n = 14) and Parkinson's disease (n = 14), and in younger adult (n = 8) and elderly (n = 8) normal controls . Although there were no differences between control groups with regard to concentrations of iron and transferrin, iron was significantly increased (p < 0 .05) in Alzheimer's disease globus pallidus and frontal cortex and Parkinson's disease globus pallidus, and transferrin was significantly increased in Alzheimer's disease frontal cortex, compared with elderly controls . The transferrin/ iron ratio, a measure of iron mobilization capacity, was decreased in globus pallidus and caudate in both disorders . Regional transferrin and iron concentrations were generally more highly correlated (Pearson's correlation coefficient) in elderly controls than in Alzheimer's and Parkinson's disease . The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders .

Alteration of Serum Concentrations of Manganese, Iron, Ferritin, and Transferrin Receptor Following Exposure to Welding Fumes Among Career Welders

“…In humans, a dysfunction in iron metabolism has been seen in IPD patients. High levels of total iron, decreased ferritin, iron-associated oxidative stress, and abnormal mitochondrial complex-I have been repeatedly reported in the postmortem substantia nigra of IPD patients (Dexter et al, 1991;Griffiths and Crossman, 1993;Loeffler et al, 1995;Sofic et al, 1991). An epidemiologic study has established that serum parameters associated with iron metabolism, such as ferritin (Ft), transferring (Tf), total iron-binding capacity, and % iron saturation, are significantly altered in IPD patients compared to normal subjects (Logroscino et al, 1997).…”

Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood–CSF barrier in vitro

“…Cellular iron overload in the basal ganglia, particularly in the substantia nigra, may catalyze the generation of reactive oxygen species and enhance lipid peroxidation. This iron-mediated oxidative stress may lead to the degeneration of nigrostriatal dopamine neurons in idiopathic Parkinson's disease patients (Jenner, 2003;Loeffler et al, 1995;Yantiri and Andersen, 1999;Youdim, 2003).…”

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

“…3 A growing body of data suggests that brain iron accumulation in vivo may contribute to tissue damage in a variety of chronic neurological disorders. Histological and magnetic resonance imaging (MRI) data have suggested increases in iron levels in the gray matter in Parkinson's disease (PD), 4 -10 Alzheimer's disease (AD), [11][12][13][14][15][16][17] multiple sclerosis (MS), 18 -21 and a host of other chronic neurological disorders. 22 Consequently, there is a growing interest in optimizing the ability of MRI to estimate iron deposition in vivo.…”