Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

BMC Neurol. 2009 Dec 22;9:63. doi: 10.1186/1471-2377-9-63.

Abstract

Background: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.

Methods: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.

Results: CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.

Conclusions: Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / blood
  • AIDS Dementia Complex / cerebrospinal fluid
  • AIDS-Related Opportunistic Infections / blood
  • AIDS-Related Opportunistic Infections / cerebrospinal fluid
  • Adult
  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Protein Precursor / blood
  • Amyloid beta-Protein Precursor / cerebrospinal fluid*
  • Analysis of Variance
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cross-Sectional Studies
  • Female
  • HIV Infections / blood
  • HIV Infections / cerebrospinal fluid*
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid*
  • Principal Component Analysis
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins