Levels of Osteopontin Protein Are Elevated in People with HIV-associated Dementia

Since the introduction of HAART, survival rates for individuals with HIV infection have markedly improved, but there has been less of an effect on HIV-associated neurocognitive disorders such as dementia.

Osteoblasts and osteoclasts on trabecula of lower jaw of calf embryo. (Photo from Wikipedia)

On the basis of previous findings, researchers at the Scripps Research Institute in La Jolla and the University of California at San Diego hypothesized that increased production of the glycoprotein osteopontin might contribute to the persistence of central nervous system (CNS) dysfunction in people with HIV. Osteopontin is a glycoprotein first identified in 1986 in osteoblasts, cells that produce bone. The results of their study appear in the September 1, 2008 issue of the Journal of Infectious Diseases.

The investigators found increased levels of osteopontin in the brains of humans with HIV encephalitis and monkeys with simian immunodeficiency virus (SIV) encephalitis. Osteopontin levels were found to be elevated in the cerebrospinal fluid of HIV-infected individuals regardless of their neuropsychological status.

However, blood plasma osteopontin levels were significantly increased in individuals with HIV-associated dementia. In addition, a longitudinal study of monkeys revealed that plasma levels of osteopontin increased before the development of SIV-induced neurological and clinical abnormalities.

Thus, the study authors concluded, plasma levels of osteopontin are significantly correlated with HIV-induced CNS dysfunction in the HAART era. This finding suggests that the development of interventions to alter osteopontin production or signaling might be beneficial in the prevention or treatment of HIV-induced CNS disorders.

In conclusion, the authors wrote, "We have shown that osteopontin levels are increased in the CSF of HIV-infected individuals and that osteopontin levels in plasma exhibit a stair-step increase across diagnostic categories of HIV-associated neurocognitive disorders."

In addition, they noted, "These findings are consistent with a pathophysiological model in which osteopontin amplifies brain macrophage accumulation, which is the pathological substrate of [HIV-associated dementia]." Furthermore, they wrote, "Longitudinal analysis of osteopontin levels in SIV-infected monkeys suggested the value of osteopontin as a plasma biomarker for neurological disease associated with AIDS."

Finally, they stated, "Thus, plasma osteopontin levels may be used, along with other criteria, to help predict the course of neurological disease in patients with AIDS. Means for decreasing osteopontin production or its signaling can be attempted therapeutically to prevent or ameliorate this disorder."

Molecular and Integrative Neurosciences Department, Scripps Research Institute, La Jolla, CA; Department of Neurosciences, AntiViral Research Center and HIV Neurobehavioral Research Center, University of California, San Diego CA.

9/05/08

Reference
TH Burdo, RJ Ellis and HS Fox. Osteopontin is increased in HIV-associated dementia. Journal of Infectious Diseases 198(5): 715-722. September 1, 2008. (Abstract).