title: Reference measurement procedure for CSF amyloid beta (Aβ)1-42and the CSF Aβ1-42/Aβ1-40ratio - a cross-validation study against amyloid PET.
abstract: A clinical diagnosis of Alzheimer's disease 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 Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures for absolute quantification of Aβ1-42in CSF. The CSF Aβ1-42/Aβ1-40ratio 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 reference measurement procedure as well as the Aβ1-42/Aβ1-40and Aβ1-42/Aβ1-38ratios in CSF, measured by high-resolution MS, with the cortical level of Aβ fibrils as measured by amyloid (18F-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 and18F-flutemetamol PET. Comparing CSF Aβ1-42concentrations with18F-flutemetamol PET showed high concordance with an area under the receiver operating characteristic curve of 0.85 and a sensitivity and specificity of 82% and 81%, respectively. The ratio of Aβ1-42/Aβ1-40or Aβ1-42/Aβ1-38significantly improved concordance with an area under the receiver operating characteristic curve of 0.95 and a sensitivity and specificity of 96% and 91%, respectively. These results show that the CSF Aβ1-42/Aβ1-40and Aβ1-42/Aβ1-38ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by18F-flutemetamol PET.
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Josef
authors: 0000-0002-3608-3819
authors: J
authors: Pannee
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Erik
authors: E
authors: Portelius
authors: Department of Clinical Sciences, Lund University, Lund, Sweden.|Memory Clinic, Department of Neurology, Skåne University Hospital, Malmö, Sweden.
authors: Lennart
authors: L
authors: Minthon
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Johan
authors: J
authors: Gobom
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Ulf
authors: U
authors: Andreasson
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.|UCL Institute of Neurology, London, UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Department of Clinical Sciences, Lund University, Lund, Sweden.|Memory Clinic, Department of Neurology, Skåne University Hospital, Malmö, Sweden.
authors: Oskar
authors: O
authors: Hansson
authors: Department of Psychiatry & Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D000682:Amyloid / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D006801:Humans; D008137:Longitudinal Studies; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012015:Reference Standards; D013548:Sweden / Q000453:epidemiology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; amyloid beta-peptides; cerebrospinal fluid; mass spectrometry; positron-emission tomography