Pittsburgh compound B imaging and cerebrospinal fluid amyloid-beta in a multicentre European memory clinic study
Por:
Leuzy, A, Chiotis, K, Hasselbalch, SG, Rinne, JO, de Mendonca, A, Otto, M, Lleo, A, Castelo-Branco, M, Santana, I, Johansson, J, Anderl-Straub, S, von Arnim, CAF, Beer, A, Blesa, R, Fortea, J, Herukka, SK, Portelius, E, Pannee, J, Zetterberg, H, Blennow, K, Nordberg, A
Publicada:
1 sep 2016
Resumen:
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-beta(42); (ii) centrally measured cerebrospinal fluid amyloid-beta(42) using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-beta(42) 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-beta production, by using the ratio of amyloid-beta(42) to amyloid-beta(40). 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-beta(42) values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-beta(42) and amyloid-beta(40)) 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-beta(42/40). 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.
Filiaciones:
Leuzy, A:
Karolinska Inst, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Chiotis, K:
Karolinska Inst, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Hasselbalch, SG:
Rigshosp, Copenhagen Univ Hosp, Danish Dementia Res Ctr, Copenhagen, Denmark
Rinne, JO:
Univ Turku, Turku Univ Hosp, Div Clin Neurosci, Turku, Finland
Univ Turku, Turku PET Ctr, Turku, Finland
de Mendonca, A:
Univ Lisbon, Fac Med, Dept Neurol, Lisbon, Portugal
Univ Lisbon, Fac Med, Lab Neurosci, Lisbon, Portugal
Otto, M:
Ulm Univ Hosp, Dept Neurol, Ulm, Germany
Lleo, A:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Castelo-Branco, M:
Brain Imaging Network Portugal, Inst Nucl Sci Appl Hlth ICNAS, Coimbra, Portugal
Univ Coimbra, Inst Biomed Imaging & Life Sci IBILI, Coimbra, Portugal
Univ Coimbra, Fac Med, Coimbra, Portugal
Santana, I:
Coimbra Univ Hosp, Dept Neurol, Coimbra, Portugal
Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol CNC, Coimbra, Portugal
Johansson, J:
Univ Turku, Turku PET Ctr, Turku, Finland
Anderl-Straub, S:
Ulm Univ Hosp, Dept Neurol, Ulm, Germany
von Arnim, CAF:
Ulm Univ Hosp, Dept Neurol, Ulm, Germany
Beer, A:
Ulm Univ Hosp, Dept Nucl Med, Ulm, Germany
Blesa, R:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Herukka, SK:
Univ Eastern Finland, Dept Neurol, Kuopio, Finland
Kuopio Univ Hosp, Kuopio, Finland
Portelius, E:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Pannee, J:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
UCL Inst Neurol, Dept Mol Neurosci, London, England
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Nordberg, A:
Karolinska Inst, Div Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden
Green Published, Hybrid Gold
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