Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV

Ronald J. Ellis, David J. Moore, Erin E. Sundermann, Robert K. Heaton, Sanjay Mehta, Todd Hulgan, David Samuels, Jerel A. Fields, Scott L. Letendre

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aβ-42, and elevated CSF total tau and neurofilament light (NFL).

METHODS: This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusions included significant CNS confounding conditions. Measurements of total tau and Aβ-42 were performed by bead suspension array. NFL and 8-oxo-dG were measured using ELISA.

RESULTS: Participants were 53 PWH, mean age 55 (±9.3) years, 19% women, and 48% non-Hispanic White. Higher 8-oxo-dG correlated with markers of AD-related neurodegeneration including lower CSF Aβ-42 (r = -0.34; p = 0.012) and higher CSF NFL (r = 0.39; p = 0.0091) and total tau (r = 0.6696; p < 0.0001). Relationships remained after adjusting for demographic variables. Levels of protein carbonyls, a marker of protein oxidation, were not related to neurodegeneration markers.

CONCLUSIONS: Among virologically suppressed PWH, nucleic acid oxidation was associated with standard CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, mitochondrial dysfunction, and specific antiretroviral drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.

Original languageEnglish (US)
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume7
Issue number6
DOIs
StatePublished - Nov 5 2020
Externally publishedYes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Multicenter Study

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