Abnormal localization of iron regulatory protein in Alzheimer's disease

• Published in: Brain research 1998-03, Vol.788 (1), p.232-236
• Main Authors: Smith, Mark A., Wehr, Kristina, Harris, Peggy L.R., Siedlak, Sandra L., Connor, James R., Perry, George
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer's disease; Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Energy Metabolism - physiology; Homeostasis; Humans; Immunohistochemistry; Iron; Iron Regulatory Protein 1; Iron Regulatory Protein 2; Iron-Regulatory Proteins; Iron-Sulfur Proteins - analysis; Medical sciences; Metabolism; Middle Aged; Nerve Tissue Proteins - analysis; Neurology; Oxidation-Reduction; Oxidative stress; Oxidative Stress - physiology; RNA-Binding Proteins - analysis
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)00002-X

A role for altered iron metabolism in the pathogenesis of Alzheimer's disease has been suggested by several reports associating the cardinal neuropathologic lesions with markers of free radical-induced damage and redox-active iron. We hypothesized that the abnormal distribution of iron in Alzheimer brain might result from alterations in iron regulatory proteins (IRP) such as IRP-1 and IRP-2, the main control elements of cellular iron homeostasis. Here, we report that while IRP-1 is present at similar levels in both Alzheimer and control brain tissue, IRP-2 shows striking differences and is associated with intraneuronal lesions, including neurofibrillary tangles, senile plaque neurites and neuropil threads. Since IRP-2 colocalizes with redox-active iron, our results suggest that alterations in IRP-2 might be directly linked to impaired iron homeostasis in Alzheimer's disease.