Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.
Title | Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Kallianpur, AR, Gittleman, H, Letendre, S, Ellis, R, Barnholtz-Sloan, JS, Bush, WS, Heaton, R, Samuels, DC, Franklin, DR, Rosario-Cookson, D, Clifford, DB, Collier, AC, Gelman, B, Marra, CM, McArthur, JC, McCutchan, JA, Morgello, S, Grant, I, Simpson, D, Connor, JR, Hulgan, T |
Corporate Authors | CHARTER Study Group |
Journal | Mol Neurobiol |
Volume | 56 |
Issue | 5 |
Pagination | 3808-3818 |
Date Published | 2019 May |
ISSN | 1559-1182 |
Keywords | Adult, Antiretroviral Therapy, Highly Active, Biomarkers, Ceruloplasmin, CHARTER, Comorbidity, Female, Haptoglobins, HIV Infections, Humans, Inflammation, Internal, Iron, Male, Multivariate Analysis, neurocognitive disorders, Regression Analysis, Vascular Endothelial Growth Factor A |
Abstract | Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder. |
DOI | 10.1007/s12035-018-1329-9 |
Alternate Journal | Mol Neurobiol |
PubMed ID | 30209774 |
PubMed Central ID | PMC6952215 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States N01 MH022005 / MH / NIMH NIH HHS / United States N01 MH22005 / / Foundation for the National Institutes of Health / U24 MH100925 / MH / NIMH NIH HHS / United States K24 MH097673 / MH / NIMH NIH HHS / United States R01 MH107345 / MH / NIMH NIH HHS / United States R01 MH095621 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States |