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 Publication2018
AuthorsKallianpur, 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 AuthorsCHARTER Study Group
JournalMol Neurobiol
Date Published09/2018
ISSN1559-1182
KeywordsInternal
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
Grant ListN01 MH22005 / / Foundation for the National Institutes of Health /
HHSN271201000036C / / Foundation for the National Institutes of Health /
HHSN271201000030C / / Foundation for the National Institutes of Health /
R01 MH107345 / / Foundation for the National Institutes of Health /
K24 MH097673 / / Foundation for the National Institutes of Health /
R01 MH095621 / / Foundation for the National Institutes of Health /
R01 MH095621 / / Foundation for the National Institutes of Health /
R01 MH107345 / / Foundation for the National Institutes of Health /