Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer's disease

Alex E. Roher, Chera L. Maarouf, Lucia I. Sue, Yiran Hu, Jeffrey Wilson, Thomas G. Beach

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Aβ1-40, Aβ1-42, total tau, phosphorylated tau, α-1 acid glycoprotein (A1GP), haptoglobin, zinc α-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of Aβ1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that Aβ1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using Aβ1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of Aβ1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Aβ1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Aβ1-42 alone. For the discrimination of AD from NADD subjects, measurement of Aβ1-42 alone was superior.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalBiomarkers
Volume14
Issue number7
DOIs
StatePublished - 2009

Keywords

  • Alzheimers-disease
  • Apolipoprotein A-1
  • Biomarkers
  • Cerebrospinal fluid
  • ELISA
  • Haemopexin
  • Haptoglobin
  • Non-Alzheimer-s disease dementias
  • Pigment epithelium-derived factor
  • Tau
  • Transthyretin
  • Zinc a-2 glycoprotein
  • α-1 acid glycoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Health, Toxicology and Mutagenesis

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