ABNORMAL LOCALIZATION OF IRON REGULATORY PROTEIN IN ALZHEIMERS-DISEASE

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 a nd redox-active iron. We hypothesized that the abnormal distribution o f iron in Alzheimer brain might result from alterations in iron regula tory 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 pre sent at similar levels in both Alzheimer and control brain tissue, IRP -2 shows striking differences and is associated with intraneuronal les ions, including neurofibrillary tangles, senile plaque neurites and ne uropil threads. Since IRP-2 colocalizes with redox-active iron, our re sults suggest that alterations in IRP-2 might be directly linked to im paired iron homeostasis in Alzheimer's disease. (C) 1998 Elsevier Scie nce B.V.