Smith, Mark A

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Abnormal localization of iron regulatory protein in Alzheimer's disease.

M A Smith; K Wehr; P L Harris; S L Siedlak; J R Connor; G Perry (Profiled Authors: Smith, Mark A; Perry, George)

Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. mas21@po.cwru.edu
Brain research 1998;788(1-2):232-6.

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.

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