P4‐537: DETECTION OF ALZHEIMER'S DISEASE IN CSF USING AUTOMATED ASSAYS FOR CLASSICAL CSF BIOMARKERSстатья из журнала
Аннотация: Use of CSF biomarkers in clinical practice is hampered by inter-laboratory variation. Automated assays aim to resolve this issue. We aimed to provide cut-points for the Elecsys® β-Amyloid(1–42) CSF, Total-Tau CSF and Phospho-Tau (181P) CSF electrochemiluminescence immunoassays (Roche Diagnostics). Participants (727 cognitively unimpaired [CU], 105 Mild Cognitive Impairment [MCI], 42 Alzheimer's disease [AD] dementia) were included from the Mayo Clinic Study of Aging (n=804) and the Mayo Clinic Alzheimer's Disease Research Center (n=70). Amyloid-beta1-42 (Aβ42), total tau (t-tau) and hyperphosphorylated tau (p-tau) were measured using the Elecsys® assays mentioned above. A subset of our participants (n=524) also underwent 11C Pittsburgh Compound B (PiB) PET imaging. Bimodal mixture modeling and the optimized Youden-index with an SUVR of 1.60 as reference value were used to create cut-points. For t-tau and p-tau we additionally created cut-points for the comparison between PiB PET amyloid positive (A+) cognitively impaired participants and amyloid negative (A-) CU participants. Optimal concordance with PiB PET was reached using either the t-tau/Aβ42 or p-tau/Aβ42 ratio. Cut-points based on the Youden index were 0.26 (95% confidence interval [CI] 0.24−0.27, agreement with PiB PET 92%) and 0.023 (0.020−0.025, agreement 92%) respectively. Other cut-points based on the Youden-index were: 893 pg/mL (791-953, agreement 79%) for Ab42, 20.8 pg/mL (18.5−23.0, agreement 74%) for p-tau and 223 pg/mL (207-257, agreement 68%) for t-tau. Mixture modeling resulted in a cut-point of 1026 pg/mL (953-1515, agreement 73%) for Aβ42, a cut-point of 25.2 pg/mL (21.0−33.3, agreement 77%) for p-tau and a cut-point of 258 pg/mL (227-350, agreement 73%) for t-tau. Comparison of cognitively impaired A+ participants with CU A- participants resulted in a cut-point of 213 (189-229) for t-tau and a cut-point of 20.8 (18.7-22.9) for p-tau using the Youden index. Concordance between CSF t-tau/Aβ42 or p-tau/Aβ42 ratios and 11C PiB PET is excellent. These markers can be used interchangeably. When one aims to categorize individual biomarkers into normal and abnormal, using the cut-point resulting from mixture modeling for Aβ42, combined with results from the CU A- vs cognitively impaired A+ groups for p-tau and t-tau may best reflect a dynamic biomarker view.
Год издания: 2019
Авторы: Argonde C. van Harten, Heather J. Wiste, Stephen D. Weigand, Michelle M. Mielke, Walter K. Kremers, Udo Eichenlaub, Richard Batrla‐Utermann, Roy B. Dyer, Alicia Algeciras‐Schimnic, David S. Knopman, Clifford R. Jack, Ronald C. Petersen
Издательство: Wiley
Источник: Alzheimer s & Dementia
Ключевые слова: Computational Drug Discovery Methods, bioluminescence and chemiluminescence research, Electrochemical Analysis and Applications
Открытый доступ: bronze
Том: 15
Выпуск: 7S_Part_29