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

Melvyn P. Heyes, Ronald J. Ellis, Lee Ryan, Meredith E. Childers, Igor Grant, Tanya Wolfson, Sarah Archibald, Terry L. Jernigan, J. Hampton Atkinson, J. Allen McCutchan, Thomas D. Marcotte, Mark R. Wallace, Scott Letendre, Rachel Schier, Robert K. Heaton, Mariana Cherner, Julie Rippeth, John Hesselink, Eliezer Masliah, Daniel R. MasysMichelle Frybarger, Ian Abramson, Reena Deustch

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of β2-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.

Original languageEnglish (US)
Pages (from-to)1033-1042
Number of pages10
JournalBrain
Volume124
Issue number5
DOIs
StatePublished - May 2001

Keywords

  • Excitotoxin
  • Human immunodeficiency virus (HIV)
  • Magnetic resonance imaging
  • Neurodegeneration

ASJC Scopus subject areas

  • Clinical Neurology

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    Heyes, M. P., Ellis, R. J., Ryan, L., Childers, M. E., Grant, I., Wolfson, T., Archibald, S., Jernigan, T. L., Atkinson, J. H., McCutchan, J. A., Marcotte, T. D., Wallace, M. R., Letendre, S., Schier, R., Heaton, R. K., Cherner, M., Rippeth, J., Hesselink, J., Masliah, E., ... Deustch, R. (2001). Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection. Brain, 124(5), 1033-1042. https://doi.org/10.1093/brain/124.5.1033