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Reference measurement procedure for CSF Aβ1-42 and the CSF Aβ1-42 /Aβ1-40 ratio - a cross-validation study against Amyloid PET.

Journal article
Authors Josef Pannee
Erik Portelius
Lennart Minthon
Johan Gobom
Ulf Andreasson
Henrik Zetterberg
Oskar Hansson
Kaj Blennow
Published in Journal of neurochemistry
Volume 139
Issue 4
Pages 651–658
ISSN 1471-4159
Publication year 2016
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 651–658
Language en
Keywords Alzheimer's disease;amyloid beta-peptides;cerebrospinal fluid;mass spectrometry;positron-emission tomography
Subject categories Neurochemistry


A clinical diagnosis of Alzheimer's disease (AD) is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for AD. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures (RMP) for absolute quantification of Aβ1-42 in CSF. The CSF Aβ1-42 /Aβ1-40 ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter-individual variations in total Aβ production. Our aim was to cross-validate the RMP as well as the Aβ1-42 /Aβ1-40 and Aβ1-42 /Aβ1-38 ratios in CSF, measured by high resolution MS, with the cortical level of Aβ fibrils as measured by amyloid ((18) F-flutemetamol) positron emission tomography (PET). We included 100 non-demented patients with cognitive symptoms from the Swedish BioFINDER study, all of whom had undergone both lumbar puncture and (18) F-flutemetamol PET. Comparing CSF Aβ1-42 concentrations with (18) F-flutemetamol PET showed high concordance with an area under the receiver operating characteristic (ROC) curve of 0.85 and a sensitivity and specificity of 82% and 81% respectively. The ratio of Aβ1-42 /Aβ1-40 or Aβ1-42 /Aβ1-38 significantly improved concordance with an area under the ROC curve of 0.95 and a sensitivity and specificity of 96% and 91% respectively. These results show that the CSF Aβ1-42 /Aβ1-40 and Aβ1-42 /Aβ1-38 ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by (18) F-flutemetamol PET. This article is protected by copyright. All rights reserved.

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