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).
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.
Buerger
Katharina
K
Department of Psychiatry, Ludwig-Maximilian University Munich, Munich, Germany. katharina.buerger@med.uni-muenchen.de
Frisoni
Giovanni
G
Uspenskaya
Olga
O
Ewers
Michael
M
Zetterberg
Henrik
H
Geroldi
Cristina
C
Binetti
Giuliano
G
Johannsen
Peter
P
Rossini
Paolo Maria
PM
Wahlund
Lars-Olof
LO
Vellas
Bruno
B
Blennow
Kaj
K
Hampel
Harald
H
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
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; D016875:tau Proteins