TY - JOUR
T1 - Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study
AU - Leuzy, Antoine
AU - Chiotis, Konstantinos
AU - Hasselbalch, Steen G
AU - Rinne, Juha O
AU - de Mendonça, Alexandre
AU - Otto, Markus
AU - Lleó, Alberto
AU - Castelo-Branco, Miguel
AU - Santana, Isabel
AU - Johansson, Jarkko
AU - Anderl-Straub, Sarah
AU - von Arnim, Christine A F
AU - Beer, Ambros
AU - Blesa, Rafael
AU - Fortea, Juan
AU - Herukka, Sanna-Kaisa
AU - Portelius, Erik
AU - Pannee, Josef
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Nordberg, Agneta
N1 - © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Aged
KW - Amyloid beta-Peptides
KW - Aniline Compounds
KW - Biomarkers
KW - Cognitive Dysfunction
KW - Dementia
KW - Enzyme-Linked Immunosorbent Assay
KW - Europe
KW - Female
KW - Humans
KW - Male
KW - Mass Spectrometry
KW - Middle Aged
KW - Peptide Fragments
KW - Positron-Emission Tomography
KW - Thiazoles
KW - Journal Article
KW - Multicenter Study
U2 - 10.1093/brain/aww160
DO - 10.1093/brain/aww160
M3 - Journal article
C2 - 27401520
SN - 0006-8950
VL - 139
SP - 2540
EP - 2553
JO - Brain
JF - Brain
IS - 9
ER -