Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI)

Exp Gerontol. 2009 Sep;44(9):579-85. doi: 10.1016/j.exger.2009.06.003. Epub 2009 Jun 16.

Abstract

Background: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported.

Methods: Six academic EADC centres recruited 49 subjects (healthy controls, subjects with mild cognitive impairment (MCI) and AD). We measured CSF beta-amyloid 42 (CSF Abeta42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma beta-amyloid 40 and 42 (Abeta40/Abeta42). Immediate fresh shipment was compared to freezing and later shipment on dry ice.

Results: CSF T-tau (fresh samples) was increased in AD versus controls (p=0.049), CSF Abeta42 (frozen samples) was decreased in MCI and AD (p=0.02), as well as plasma Abeta40 (fresh and frozen samples) in AD (p=0.049 and p=0.016). Pooled values of neurochemical parameters and ratios thereof were different between centres (p<0.005). Analysis of frozen samples yielded higher diagnostic accuracy than immediate fresh shipment with 100% (fresh: 100%) correctly classified in control subjects, 100% (78%) in MCI, 91% (91%) in AD.

Conclusion: The use of frozen rather than fresh samples renders higher diagnostic accuracy within a multicentre context. We confirmed the feasibility of a multicentre AD biomarker programme for future clinical trials.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / blood
  • Apolipoproteins E / cerebrospinal fluid
  • Biomarkers / blood*
  • Biomarkers / cerebrospinal fluid*
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments* / blood
  • Peptide Fragments* / cerebrospinal fluid
  • Pilot Projects
  • Positron-Emission Tomography / methods*
  • Reproducibility of Results
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Biomarkers
  • Peptide Fragments
  • tau Proteins