Leuzy Antoine, Chiotis Konstantinos, Hasselbalch Steen G, Rinne Juha O, de Mendonça Alexandre, Otto Markus, Lleó Alberto, Castelo-Branco Miguel, Santana Isabel, Johansson Jarkko, Anderl-Straub Sarah, von Arnim Christine A F, Beer Ambros, Blesa Rafael, Fortea Juan, Herukka Sanna-Kaisa, Portelius Erik, Pannee Josef, Zetterberg Henrik, Blennow Kaj, Nordberg Agneta
1 Department of Neurobiology, Care Science, and Society, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
2 Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Brain. 2016 Sep;139(Pt 9):2540-53. doi: 10.1093/brain/aww160. Epub 2016 Jul 7.
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.
本研究的目的是评估使用匹兹堡化合物B正电子发射断层扫描得出的脑淀粉样变性数据与以下各项之间的一致性：(i) 使用多实验室INNOTEST酶联免疫吸附测定法得出的脑脊液淀粉样β蛋白42（Aβ42）浓度；(ii) 使用Meso Scale Discovery酶联免疫吸附测定法进行中心测量的脑脊液Aβ42；以及(iii) 使用基于抗体独立质谱的参考方法进行中心测量的脑脊液Aβ42。此外，我们通过使用Aβ42与Aβ40的比率来检验以下假设，即淀粉样生物标志物测量之间的不一致可能是由于总Aβ产生的个体差异所致。我们的研究人群包括来自七个中心的243名受试者，这些中心属于阿尔茨海默病和帕金森病生物标志物倡议组织，包括认知正常的受试者以及患有轻度认知障碍、阿尔茨海默病痴呆、额颞叶痴呆和血管性痴呆的患者。所有受试者均有匹兹堡化合物B正电子发射断层扫描数据、脑脊液INNOTEST Aβ42值以及可供重新分析的脑脊液样本。使用Meso Scale Discovery电化学发光酶联免疫吸附测定技术以及一种新型的、抗体独立的质谱参考方法对脑脊液样本进行重新分析（检测Aβ42和Aβ40）。匹兹堡化合物B标准化摄取值比率结果采用Centiloid方法进行标度。在轻度认知障碍和阿尔茨海默病受试者中，Meso Scale Discovery/质谱参考测量程序结果与匹兹堡化合物B之间的一致性较高，而在认知正常和非阿尔茨海默病组中观察到的结果则更具变异性。当使用Aβ42/40时，匹兹堡化合物B分类与Meso Scale Discovery/质谱参考测量程序结果之间的一致性进一步提高。匹兹堡化合物B视觉评级与Centiloids之间的一致性近乎完全。尽管匹兹堡化合物B与中心分析的脑脊液之间的一致性有所提高，但仍有少数受试者表现出不一致的结果。虽然未来还需要进行研究，但我们的结果表明，在某些个体中，淀粉样生物标志物结果可能不可互换。
