TY - JOUR
T1 - Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV
AU - Ellis, Ronald J.
AU - Moore, David J.
AU - Sundermann, Erin E.
AU - Heaton, Robert K.
AU - Mehta, Sanjay
AU - Hulgan, Todd
AU - Samuels, David
AU - Fields, Jerel A.
AU - Letendre, Scott L.
N1 - Publisher Copyright:
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/11/5
Y1 - 2020/11/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093476458&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85093476458&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000902
DO - 10.1212/NXI.0000000000000902
M3 - Article
C2 - 33055205
AN - SCOPUS:85093476458
SN - 2332-7812
VL - 7
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 6
ER -
