BACKGROUND: The increasing role of cerebrospinal fluid (CSF) biomarkers in the early diagnosis of Alzheimer's disease (AD) is reflected in recently published diagnostic and/or research criteria. A growing body of evidence suggests better diagnostic performance of the amyloid-β (Aβ)42/40 CSF concentration ratio compared to the Aβ42 concentration alone. OBJECTIVE: (a) to analytically validate two novel ELISAs capable to measure Aβ1-40 and Aβ1-42 in the CSF, and (b) to compare the diagnostic accuracies of Aβ1-42 and Aβ42/40 ratio. METHODS: In this study, (a) the novel Aβ1-40 and Aβ1-42 ELISAs (IBL International GmbH, Hamburg, Germany) have been analytically validated, and (b) a clinical study has been performed comparing the diagnostic performance of the CSF Aβ42/40 concentration ratio and the CSF Aβ42 concentration. RESULTS: In the analytical part of the study, only marginal cross-reactivity (Aβ1-42 versus Aβ1-40) was observed; recoveries were in the range of 85-100% for the samples diluted 1 : 20-1 : 640 (Aβ1-40), and 92-104% for the samples diluted 1 : 20-1 : 320 (Aβ1-42). For Aβ1-40, the intra-assay imprecision was 2.1%, the inter-assay imprecision was 4.4%, and the inter-lot imprecision was 5.4 %. For Aβ1-42, the numbers were 3.1%, 6.2%, and 6.9%, respectively. The goodness of the fit of the average standard curves was >0.99 for both assays, and the imprecision of the optical densities in ten repetitions of the standard curves was ≤5% for all standards. In the clinical part, at the cut off value 691 pg/mL, Aβ1-42 showed sensitivity and specificity of 69.3% and 88.9%, respectively, whereas at the cut off value 0.06, the Aβ42/40 ratio showed significantly improved performance with sensitivity and specificity of 93.3% and 100%, respectively. The area under the ROC curve for Aβ42/40 (0.974) was highly significantly larger compared to Aβ1-42 concentration ROC curve (0.827, p < 0.0001). CONCLUSIONS: (a) the novel Aβ1-40 and Aβ1-42 ELISA assays characterize with very good analytical performance; (b) we reconfirm that the CSF Aβ42/40 concentration ratio shows significantly better diagnostic performance compared to the CSF Aβ1-42 concentration alone.
BACKGROUND: The increasing role of cerebrospinal fluid (CSF) biomarkers in the early diagnosis of Alzheimer's disease (AD) is reflected in recently published diagnostic and/or research criteria. A growing body of evidence suggests better diagnostic performance of the amyloid-β (Aβ)42/40 CSF concentration ratio compared to the Aβ42 concentration alone. OBJECTIVE: (a) to analytically validate two novel ELISAs capable to measure Aβ1-40 and Aβ1-42 in the CSF, and (b) to compare the diagnostic accuracies of Aβ1-42 and Aβ42/40 ratio. METHODS: In this study, (a) the novel Aβ1-40 and Aβ1-42 ELISAs (IBL International GmbH, Hamburg, Germany) have been analytically validated, and (b) a clinical study has been performed comparing the diagnostic performance of the CSF Aβ42/40 concentration ratio and the CSF Aβ42 concentration. RESULTS: In the analytical part of the study, only marginal cross-reactivity (Aβ1-42 versus Aβ1-40) was observed; recoveries were in the range of 85-100% for the samples diluted 1 : 20-1 : 640 (Aβ1-40), and 92-104% for the samples diluted 1 : 20-1 : 320 (Aβ1-42). For Aβ1-40, the intra-assay imprecision was 2.1%, the inter-assay imprecision was 4.4%, and the inter-lot imprecision was 5.4 %. For Aβ1-42, the numbers were 3.1%, 6.2%, and 6.9%, respectively. The goodness of the fit of the average standard curves was >0.99 for both assays, and the imprecision of the optical densities in ten repetitions of the standard curves was ≤5% for all standards. In the clinical part, at the cut off value 691 pg/mL, Aβ1-42 showed sensitivity and specificity of 69.3% and 88.9%, respectively, whereas at the cut off value 0.06, the Aβ42/40 ratio showed significantly improved performance with sensitivity and specificity of 93.3% and 100%, respectively. The area under the ROC curve for Aβ42/40 (0.974) was highly significantly larger compared to Aβ1-42 concentration ROC curve (0.827, p < 0.0001). CONCLUSIONS: (a) the novel Aβ1-40 and Aβ1-42 ELISA assays characterize with very good analytical performance; (b) we reconfirm that the CSF Aβ42/40 concentration ratio shows significantly better diagnostic performance compared to the CSF Aβ1-42 concentration alone.
Authors: Burcu F Darst; Rebecca L Koscik; Annie M Racine; Jennifer M Oh; Rachel A Krause; Cynthia M Carlsson; Henrik Zetterberg; Kaj Blennow; Bradley T Christian; Barbara B Bendlin; Ozioma C Okonkwo; Kirk J Hogan; Bruce P Hermann; Mark A Sager; Sanjay Asthana; Sterling C Johnson; Corinne D Engelman Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Piotr Lewczuk; Johannes Kornhuber; Jon B Toledo; John Q Trojanowski; Malgorzata Knapik-Czajka; Oliver Peters; Jens Wiltfang; Leslie M Shaw Journal: J Alzheimers Dis Date: 2015 Impact factor: 4.472
Authors: Piotr Lewczuk; Peter Riederer; Sid E O'Bryant; Marcel M Verbeek; Bruno Dubois; Pieter Jelle Visser; Kurt A Jellinger; Sebastiaan Engelborghs; Alfredo Ramirez; Lucilla Parnetti; Clifford R Jack; Charlotte E Teunissen; Harald Hampel; Alberto Lleó; Frank Jessen; Lidia Glodzik; Mony J de Leon; Anne M Fagan; José Luis Molinuevo; Willemijn J Jansen; Bengt Winblad; Leslie M Shaw; Ulf Andreasson; Markus Otto; Brit Mollenhauer; Jens Wiltfang; Martin R Turner; Inga Zerr; Ron Handels; Alexander G Thompson; Gunilla Johansson; Natalia Ermann; John Q Trojanowski; Ilker Karaca; Holger Wagner; Patrick Oeckl; Linda van Waalwijk van Doorn; Maria Bjerke; Dimitrios Kapogiannis; H Bea Kuiperij; Lucia Farotti; Yi Li; Brian A Gordon; Stéphane Epelbaum; Stephanie J B Vos; Catharina J M Klijn; William E Van Nostrand; Carolina Minguillon; Matthias Schmitz; Carla Gallo; Andrea Lopez Mato; Florence Thibaut; Simone Lista; Daniel Alcolea; Henrik Zetterberg; Kaj Blennow; Johannes Kornhuber Journal: World J Biol Psychiatry Date: 2017-10-27 Impact factor: 4.132
Authors: Magdalena Korecka; Michal J Figurski; Susan M Landau; Magdalena Brylska; Jacob Alexander; Kaj Blennow; Henrik Zetterberg; William J Jagust; John Q Trojanowski; Leslie M Shaw Journal: Clin Chem Date: 2020-04-01 Impact factor: 8.327