Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection

Neuronal injury, dendritic loss and brain atrophy are frequent complication s of infection with human immunodeficiency virus (HIV) type 1, Activated br ain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contrib utes to neuronal injury and cerebral volume loss. In the present cross-sect ional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid con centrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) b ut not in regions relatively resistant to excitotoxicity (the non-limbic co rtex, thalamus and white matter). Increased CSF quinolinic acid concentrati ons also correlated with higher CSF HIV-1 RNA levels. In support of the spe cificity of these associations, blood levels of quinolinic acid were unrela ted to striatal and limbic volumes, and CSF levels of beta (2-)microglobuli n, a non-specific and non-excitotoxic marker of immune activation, were unr elated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes t o atrophy in vulnerable brain regions in HIV infection and that virus repli cation is a significant driver of local quinolinic acid biosynthesis.