Alzheimer’s disease (AD) is a common type of dementia causing memory loss and cognitive functional impairment of aged patients. Chronic inflammation of the brain might be attributed to the pathology of AD, which includes the deposition of amyloid-beta (Aβ). Osteopontin (OPN), encoded by secreted phosphoprotein 1 (Spp1), is a pro-inflammatory molecule that regulates the secretion of various cytokines to mediate inflammation. It is revealed that OPN level in cerebrospinal fluid is elevated in AD patients. However, the role of OPN in AD pathology is unclear. In this project, I have characterized the Spp1/OPN expression in the cerebral cortices of wildtype (WT) and AD transgenic (APP/PS1) mice at by establishing the Spp1 expression profile and studying the cellular expression of OPN...[ Read more ]

Alzheimer’s disease (AD) is a common type of dementia causing memory loss and cognitive functional impairment of aged patients. Chronic inflammation of the brain might be attributed to the pathology of AD, which includes the deposition of amyloid-beta (Aβ). Osteopontin (OPN), encoded by secreted phosphoprotein 1 (Spp1), is a pro-inflammatory molecule that regulates the secretion of various cytokines to mediate inflammation. It is revealed that OPN level in cerebrospinal fluid is elevated in AD patients. However, the role of OPN in AD pathology is unclear. In this project, I have characterized the Spp1/OPN expression in the cerebral cortices of wildtype (WT) and AD transgenic (APP/PS1) mice at by establishing the Spp1 expression profile and studying the cellular expression of OPN in their brain. Real-time qPCR analysis of the cerebral cortices of 12-month-old WT and APP/PS1 mice was performed and revealed a three-fold increase of Spp1 relative mRNA level in APP/PS1 mice compared to WT mice. To examine the cellular localization of induced OPN expression in the disease model, I performed immunofluorescence analysis of OPN in cerebral cortex of 12-month-old WT and APP/PS1 mice. Remarkably, while OPN expression was low in the glial cells in WT mice, protein expression was induced in microglia in the cerebral cortex of APP/PS1 mice. OPN was majorly expressed in a small population of phagocytic microglia when highly associated with Aβ. Moreover, CD44, the OPN receptor, was expressed in activated astrocytes in 12-month-old APP/PS1 mouse cerebral cortex, which was barely observed in age-matched WT mice. The results suggested OPN may involve in the changes in the functions of microglia upon the stimulation of Aβ, and act as a signaling cytokine to facilitate the communication between microglia and astrocytes in AD pathology.