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

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 7; no. 6; p. e902
• Main Authors: Ellis, Ronald J, Moore, David J, Sundermann, Erin E, Heaton, Robert K, Mehta, Sanjay, Hulgan, Todd, Samuels, David, Fields, Jerel A, Letendre, Scott L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Academy of Neurology 05.11.2020; Lippincott Williams & Wilkins
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000000902

OBJECTIVETo 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). METHODSThis 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. RESULTSParticipants 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. CONCLUSIONSAmong 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 EVIDENCEThis study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.