PMID- 28358733
OWN - NLM
STAT- MEDLINE
DCOM- 20180219
LR  - 20220321
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 31
IP  - 10
DP  - 2017 Jun 19
TI  - Plasma dickkopf-related protein 1, an antagonist of the Wnt pathway, is 
      associated with HIV-associated neurocognitive impairment.
PG  - 1379-1385
LID - 10.1097/QAD.0000000000001481 [doi]
AB  - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: DKK1 is a specific biomarker for NCI in 
      HIV adults, implicating the Wnt pathway in HIV neuropathogenesis.
FAU - Yu, Chunjiang
AU  - Yu C
AD  - aDepartment of Immunology and Microbiology, Rush University Medical Center, 
      Chicago, Illinois bDepartment of Medicine cDepartment of Psychiatry University of 
      California, San Diego, California, USA.
FAU - Seaton, Melanie
AU  - Seaton M
FAU - Letendre, Scott
AU  - Letendre S
FAU - Heaton, Robert
AU  - Heaton R
FAU - Al-Harthi, Lena
AU  - Al-Harthi L
LA  - eng
GR  - R01 DA033966/DA/NIDA NIH HHS/United States
GR  - K24 MH097673/MH/NIMH NIH HHS/United States
GR  - P50 DA026306/DA/NIDA NIH HHS/United States
GR  - R01 MH100628/MH/NIMH NIH HHS/United States
GR  - R01 NS060632/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Biomarkers)
RN  - 0 (DKK1 protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - AIDS Dementia Complex/*pathology
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers/*blood
MH  - California
MH  - Female
MH  - HIV Infections/*complications/*pathology
MH  - Humans
MH  - Immunoassay
MH  - Intercellular Signaling Peptides and Proteins/*blood
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Plasma/*chemistry
MH  - Young Adult
PMC - PMC5472066
MID - NIHMS865494
COIS- Author conflict of interest: None of the authors have a financial or ethical 
      conflict of interest relevant to this study
EDAT- 2017/03/31 06:00
MHDA- 2018/02/20 06:00
PMCR- 2018/06/19
CRDT- 2017/03/31 06:00
PHST- 2017/03/31 06:00 [pubmed]
PHST- 2018/02/20 06:00 [medline]
PHST- 2017/03/31 06:00 [entrez]
PHST- 2018/06/19 00:00 [pmc-release]
AID - 10.1097/QAD.0000000000001481 [doi]
PST - ppublish
SO  - AIDS. 2017 Jun 19;31(10):1379-1385. doi: 10.1097/QAD.0000000000001481.