Abstract
Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimers disease (AD) compared with agematched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-β load (r2 = 0.25; P < 0.05; n = 20) and aging (r2 = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-β load, but not age. While the functional consequences of this amyloid-β associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-β generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD.
Keywords: Osteopontin, tumorigenesis, remodeling, repair, inflammation, amyloid-β, neuron, Alzheimer's disease, aging, cell cycle
Current Alzheimer Research
Title: Increased Expression of the Remodeling- and Tumorigenic-Associated Factor Osteopontin in Pyramidal Neurons of the Alzheimers Disease Brain
Volume: 4 Issue: 1
Author(s): John K. Wung, George Perry, Aaron Kowalski, Peggy L. R. Harris, Glenda M. Bishop, Mehu A. Trivedi, Sterling C. Johnson, Mark A. Smith, David T. Denhardt and Craig S. Atwood
Affiliation:
Keywords: Osteopontin, tumorigenesis, remodeling, repair, inflammation, amyloid-β, neuron, Alzheimer's disease, aging, cell cycle
Abstract: Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimers disease (AD) compared with agematched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-β load (r2 = 0.25; P < 0.05; n = 20) and aging (r2 = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-β load, but not age. While the functional consequences of this amyloid-β associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-β generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD.
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Cite this article as:
Wung K. John, Perry George, Kowalski Aaron, R. Harris L. Peggy, Bishop M. Glenda, Trivedi A. Mehu, Johnson C. Sterling, Smith A. Mark, Denhardt T. David and Atwood S. Craig, Increased Expression of the Remodeling- and Tumorigenic-Associated Factor Osteopontin in Pyramidal Neurons of the Alzheimers Disease Brain, Current Alzheimer Research 2007; 4 (1) . https://dx.doi.org/10.2174/156720507779939869
DOI https://dx.doi.org/10.2174/156720507779939869 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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