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. Author manuscript; available in PMC: 2016 Jul 8.
Published in final edited form as: Nat Rev Neurol. 2016 Mar 11;12(4):234–248. doi: 10.1038/nrneurol.2016.27

Table 2.

Surrogate biomarkers for cognitive status in HIV

Pathophysiological mechanism Primary infection ANI/MND HIV-associated dementia
Cell stress Not determined

  • CSF sphingomyelin* (REFS 72,75,76)

    CSF ceramide* (REFS 72,75,76)

  • CSF esterified cholesterols* (REFS 75,76); sphingomyelinase activity76

  • CSF hydroxynonenals72

  • Brain and CSF sphingomyelin72

  • Brain and CSF ceramide72
Neuronal injury/protection

  • CSF NFL95

  • CSF p-tau95

  • CSF β-amyloid95

  • Brain NAA224

 Not determined
Oxidative stress Not determined

  • CSF haem oxygenase-1* (REF. 142)

  • CSF hydroxynonenals72,227

  • CSF protein carbonyls228

  • CSF haem oxygenase-1 (REF. 142)

  • Brain SOD-1 (REF. 229)

  • Brain iNOS229

  • CSF 3-nitrotyrosine230

  • CSF protein carbonyls228
Energy metabolism Brain choline57,224

  • CSF Krebs cycle substrates*‡§ (REF. 73)

  • CSF triglycerides‡ (REF. 75)

  • CSF fatty acids* (REF. 76)

 Brain choline79
Immune activation

  • Plasma sCD163 (REF. 56)

  • Brain myo-inositol224

  • Plasma IL-1α, IL 12, TNF, lymphotoxin, IL-10, IP-10, MCP-3, eotaxin, IFN-α17

  • Plasma MMP 2 (REF. 55)

  • Brain HLA-DR72

  • Panel of cytokines from plasma and CSF*‡§ (REF. 96)

  • Plasma65 and CSF67 sCD14

  • Plasma sCD163 (REF. 66)

  • CSF MCP-1 (REFS 231,232)

  • Plasma TNF231

  • Brain HLA-DR72

  • Brain myo-inositol70,79

  • Plasma sCD14 (REFS 65,233)

  • CSF neopterin66,234

  • CSF osteopontin235

  • CSF fractalkine236

  • Brain IL-1β229

  • Brain IL-10 (REF. 229)

  • Brain STAT-1 (REF. 237)

  • CSF S100β238
Glutamate regulation Brain glutamate224

  • Brain glutamate* (REF. 77)

  • CSF glutamine*‡ (REF. 73)

  • Brain Glx70

  • Brain glutaminase C237

ANI, asymptomatic neurocognitive impairment; sCD, soluble cluster of differentiation; CSF, cerebrospinal fluid; Glx, glutamate/glutamine complex; HLA DR, human leukocyte antigen–antigen D related; IFN, interferon; iNOS, inducible nitrous oxide synthase; IP, inducible protein; MCP, monocyte specific chemokine; MMP, matrix metalloprotease; MND, mild neurocognitive disorder; NAA, N-acetyl aspartate; NFL, neurofilament light chain; p-tau, phosphorylated tau; sAPPβ, soluble amyloid precursor protein beta; STAT, signal transducers and activators of transcription; SOD 1, superoxide dismutase 1; TNF, tumour necrosis factor; t-tau, total tau.

*

Changes in these markers indicate cognitive decline in HIV+ patients.

‡

Changes in these markers indicate cognitive improvement in HIV+ patients.

§

Some of the tested molecules were associated with cognitive decline, some with cognitive improvement.