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 A beta 42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma p-amyloid 40 and 42 (A beta 40/A beta 42). 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 A beta A2 (frozen samples) was decreased in MCI and AD (p = 0.02), as well as plasma A beta 40 (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. (C) 2009 Elsevier Inc. All rights reserved.