Abnormal localization of iron regulatory protein in Alzheimer's 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 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.
Smith
M A
MA
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. mas21@po.cwru.edu
Wehr
K
K
Harris
P L
PL
Siedlak
S L
SL
Connor
J R
JR
Perry
G
G
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000032:analysis*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000032:analysis*
D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2