title: Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.
abstract: The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference measurement procedure findings was further improved when using amyloid-β42/40 Agreement between Pittsburgh compound B visual ratings and Centiloids was near complete. Despite improved agreement between Pittsburgh compound B and centrally analysed cerebrospinal fluid, a minority of subjects showed discordant findings. While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals.
authors.affiliation: 1 Department of Neurobiology, Care Science, and Society, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.affiliation: 1 Department of Neurobiology, Care Science, and Society, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Chiotis
authors.affiliation: 2 Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
authors.affiliation: 3 Division of Clinical Neurosciences, Turku University Hospital, University of Turku, Turku, Finland 4 Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: 5 Department of Neurology and Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Mendonça
authors.affiliation: 6 Department of Neurology, Ulm University Hospital, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.affiliation: 7 Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de Sant Pau, Barcelona, Spain 8 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.affiliation: 9 Institute for Nuclear Sciences Applied to Health (ICNAS), Brain Imaging Network of Portugal, Coimbra, Portugal 10 Institute for Biomedical Imaging and Life Sciences (IBILI) and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Castelo-Branco
authors.affiliation: 11 Department of Neurology, Coimbra University Hospital, Coimbra, Portugal 12 Centre for Neuroscience and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: 4 Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Johansson
authors.affiliation: 6 Department of Neurology, Ulm University Hospital, Ulm, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Anderl-Straub
authors.affiliation: 6 Department of Neurology, Ulm University Hospital, Ulm, Germany.
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
authors.affiliation: 13 Department of Nuclear Medicine, Ulm University Hospital, Ulm, Germany.
authors.forename: Ambros
authors.initials: A
authors.lastname: Beer
authors.affiliation: 7 Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de Sant Pau, Barcelona, Spain 8 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: 7 Department of Neurology, Institut d'Investigacions Biomèdiques, Hospital de Sant Pau, Barcelona, Spain 8 Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: 14 Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sanna-Kaisa
authors.initials: SK
authors.lastname: Herukka
authors.affiliation: 15 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: 15 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Josef
authors.initials: J
authors.lastname: Pannee
authors.affiliation: 15 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden 16 Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: 15 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: 1 Department of Neurobiology, Care Science, and Society, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden 17 Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden agneta.k.nordberg@ki.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000814:Aniline Compounds; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000378:metabolism*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C538897:amyloid beta-protein (40-42)
keywords: Alzheimer’s disease; CSF Aβ42; CSF Aβ42/40; Centiloids; PiB PET