title: 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).
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Ludwig-Maximilian University Munich, Munich, Germany. katharina.buerger@med.uni-muenchen.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Buerger
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frisoni
authors.forename: Olga
authors.initials: O
authors.lastname: Uspenskaya
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Cristina
authors.initials: C
authors.lastname: Geroldi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Peter
authors.initials: P
authors.lastname: Johannsen
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins