Collectively, we and others have shown that the multifunctional proinflammatory cytokine-like protein osteopontin (OPN) is elevated in the plasma, cerebrospinal fluid, and brain tissue of HIV-infected individuals with moderate to severe cognitive impairment (Burdo et al., 2007, Burdo et al., 2008, Brown et al., 2011, Marcondes et al., 2014). This evidence concerns the gene SPP1 and Cognitive impairment.