title: Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.
abstract: OBJECTIVE
  To investigate the role of homocysteine in neuronal injury in HIV infection.
  
  
  METHODS
  Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation.
  
  
  RESULTS
  A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016).
  
  
  CONCLUSIONS
  A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Ahlgren
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars-Magnus
authors.initials: LM
authors.lastname: Andersson
authors.affiliation: Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.|UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D005492:Folic Acid / Q000097:blood; D015658:HIV Infections / Q000097:blood* / Q000134:cerebrospinal fluid / Q000188:drug therapy; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D009474:Neurons / Q000473:pathology*; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12