Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease.
Membrane and cytoskeletal structures are known targets of oxidative injury. Brains from patients with Alzheimer's disease have cytoskeletal abnormalities and platelet and possible neuronal membrane lesions. The authors have recently demonstrated that superoxide anion is a powerful inducer of heat-shock protein synthesis, and have also shown that in response to oxidative stress or hyperthermia, intracellular levels of antioxidant enzymes increase to several folds. Whether the aforementioned mechanisms play a role in Alzheimer's disease has been suggested but is not totally established. While exploring this possibility, tissue sections from five brains with Alzheimer's disease and five neuropathologically normal age-matched controls were immunostained with polyclonal antibodies against superoxide dismutase (CuZn- and Mn- forms) and catalase. A standard avidin-biotin-peroxidase method was used for antigen detection. A subgroup of neurofibrillary tangles (15-25%) and senile plaques (50%) showed immunoreactivity for both enzymes with a staining pattern similar (but not identical) to that usually observed with antibodies against ubiquitin. Senile plaques displayed a granular pattern of immunostaining. Amyloid cores in mature classical plaques remained unstained. In addition, occasional elements with features consistent with reactive glial cells were strongly immunostained. Tangle-free neurons in both diseased and control brains showed weak to absent intracytoplasmic immunoreactivity. The immunoreactivity was totally abolished by preincubation of the primary antibodies with the corresponding purified antigens. These findings support the hypothesis that oxidative stress may be involved in the pathogenesis of Alzheimer's disease.
Department of Pathology, New York Medical College, Valhalla.
M A
MA
Pappolla
R A
RA
Omar
K S
KS
Kim
N K
NK
Robakis
D000544:Alzheimer Disease / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D002374:Catalase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016874:Neurofibrillary Tangles / Q000201:enzymology; D013194:Staining and Labeling; D013482:Superoxide Dismutase / Q000378:metabolism*
D002374:Catalase; D013482:Superoxide Dismutase