Publication Abstract Display | Type: Published Manuscript | Title: Cerebrospinal Fluid Ceruloplasmin,
Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with
Neurocognitive Impairment in Adults with HIV Infection. | Authors: Kallianpur AR, Gittleman H, Letendre S, Ellis R, Barnholtz-Sloan JS, Bush WS,
Heaton R, Samuels DC, Franklin DR Jr, 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; CHARTER Study Group | Year: 2019 | Publication: Molecular Neurobiology | Volume: 56 Issue: 5 Pages: 3808-3818 | 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. |
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