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N. V. Hunter, D. Aggarwal, F. N. Ross- Cisneros, A. A. Sadun; Immunohistochemical Evaluation of S100A12 (Calgranulin C) in Alzheimer Disease Optic Nerves. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4028.
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S100A12 belongs to the S100 family of calcium-binding proteins. Of this S100 family, S100A2 which can be released by brain macrophages, microglia, and neutrophils in microvasculature , and can act as a ligand to the receptor for advanced glycation end products (RAGE). S100A12 has been shown to be involved with inflammation, the initiation of amyloidosis, and high-molecular-weight insoluble protein aggregates, in the brains of Alzheimer’s disease (AD) patients. Therefore, the aim of this study was to investigate the presence of S100A12 (Calgranulin C) in AD optic nerves for its possible role in optic neuropathy.
Optic nerve specimens were obtained at autopsy from twelve patients with AD and compared to six normal age-matched control tissues. AD tissues were supplied by our Alzheimer’s Disease Research Center (ADRC) and controls were purchased through local eye banks. Tissues were immersion fixed in neutral buffered formalin, dissected into cross-sectional profiles just proximal to the globe, then processed and embedded into paraffin blocks. Sections were cut at 5 µm and immunostained, using an indirect method with horseradish peroxidase and diaminobenzidine as the substrate-chromogen, with a mouse anti-human S100A12 monoclonal antibody at a dilution of 1:50. Light microscopic images were viewed on a Zeiss Axioskop microscope and captured by a digital camera and saved to a computer.
Immunoreactivity for S100A12 in AD optic nerves appeared as circular plaque-like structures of various sizes often possessing an eccentrically placed large vacuole, "punctate" staining in the cytoplasm of glial cells, and axonal elements. The brains of the same patients demonstrated similar plaque-like structures staining positive for S100A12. In contrast, age matched controls demonstrated very little staining for S100A12 (Calgranulin C) protein in optic nerves and brains.
S100A12 was identified immunohistochemically in the optic nerves of AD patients. The pattern of staining suggests that S100A12 is associated with a plaque-like structure similar to lesions found in the brains of the same patients. Thus, our findings suggest that S100A12 may play a role in activation of the RAGE pathway toward inflammation, protein aggregate, and plaque formation associated with AD optic neuropathy.
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