title: Plasma dickkopf-related protein 1, an antagonist of the Wnt pathway, is associated with HIV-associated neurocognitive impairment.
abstract: Dickkopf-related protein 1 (DKK1) is a soluble antagonist of the Wningless (Wnt) pathway. It binds to and sequesters low-density lipoprotein receptor-related proteins 5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV-positive (HIV) individuals. We evaluated, here, the relationship between plasma DKK1 and global NCI.
  
  
  
  Plasma samples and data from 41 HIV to 42 HIV adults were obtained from the University of California, San Diego, California, USA. Concentrations of DKK1 and a comparator protein, monocyte chemoattractant protein-1 (MCP-1), were quantified in plasma by immunoassay. All study participants completed a standardized comprehensive neuropsychological test battery and their performance was summarized using the global deficit score method.
  
  
  
  A higher DKK1 level was associated with NCI among HIV participants (d = 0.63, P = 0.05), particularly among the 26 participants whose plasma HIV RNA level was suppressed (d = 0.74, P = 0.08). DKK1 level was not associated with NCI among HIV participants (P = 0.98). was not associated with NCI in either group. In HIV adults with suppressed plasma HIV RNA, a receiver operator characteristic curve identified that a DKK1 level of at least 735 pg/ml had a positive predictive value of 83.3% for a diagnosis of NCI. This association did not weaken after accounting for the effect of AIDS, nadir CD4 T-cell count, addictive drug use, or demographic characteristics.
  
  
  
  DKK1 is a specific biomarker for NCI in HIV adults, implicating the Wnt pathway in HIV neuropathogenesis.
authors.affiliation: aDepartment of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois bDepartment of Medicine cDepartment of Psychiatry University of California, San Diego, California, USA.
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Yu
authors.forename: Melanie
authors.initials: M
authors.lastname: Seaton
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Robert
authors.initials: R
authors.lastname: Heaton
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002140:California; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007118:Immunoassay; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010949:Plasma / Q000737:chemistry*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins