Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

TitleCerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.
Publication TypeJournal Article
Year of Publication2019
AuthorsKallianpur, AR, Gittleman, H, Letendre, S, Ellis, RJ, Barnholtz-Sloan, JS, Bush, WS, Heaton, RK, Samuels, DC, Franklin, D, Rosario-Cookson, D, Clifford, DB, Collier, AC, Gelman, B, Marra, CM, McArthur, JC, McCutchan, JA, Morgello, S, Grant, I, Simpson, DM, Connor, JR, Hulgan, T
Corporate AuthorsCHARTER Group
JournalMol Neurobiol
Volume56
Issue5
Pagination3808-3818
Date Published2019 May
ISSN1559-1182
KeywordsAdult, 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.

DOI10.1007/s12035-018-1329-9
Alternate JournalMol. Neurobiol.
PubMed ID30209774
PubMed Central IDPMC6952215
Grant ListU24 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