Immunohistochemical evidence of antioxidant stress in Alzheimer's disease

Miguel Pappolla, R. A. Omar, K. S. Kim, N. K. Robakis

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)621-628
Number of pages8
JournalAmerican Journal of Pathology
Volume140
Issue number3
StatePublished - Mar 1992
Externally publishedYes

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Alzheimer Disease
Antioxidants
Amyloid Plaques
Antibodies
Oxidative Stress
Antigens
Neurofibrillary Tangles
Membranes
Avidin
Brain
Brain Diseases
Enzymes
Biotin
Ubiquitin
Heat-Shock Proteins
Amyloid
Neuroglia
Superoxides
Catalase
Peroxidase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Immunohistochemical evidence of antioxidant stress in Alzheimer's disease. / Pappolla, Miguel; Omar, R. A.; Kim, K. S.; Robakis, N. K.

In: American Journal of Pathology, Vol. 140, No. 3, 03.1992, p. 621-628.

Research output: Contribution to journalArticle

Pappolla, Miguel ; Omar, R. A. ; Kim, K. S. ; Robakis, N. K. / Immunohistochemical evidence of antioxidant stress in Alzheimer's disease. In: American Journal of Pathology. 1992 ; Vol. 140, No. 3. pp. 621-628.
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