BACKGROUND: The assessment of total tau, phosphorylated tau (pTau-181) and amyloid beta (Aβ 1-42) concentrations in the cerebrospinal fluid (CSF) of subjects has been validated for the diagnosis of Alzheimer's disease (AD). Although these measurements have shown some variability, little is known about their intersite variability in clinical settings. METHODS: A total of 880 subjects (AD, n = 515; non-AD, n = 365) from three French memory centers were included. Receiver-operating characteristic analyses were performed to computerized area under curves (AUCs) and optimal thresholds for each biomarker in the three centers. A test-retest study was performed in a group of 32 CSF samples by repeated blind analysis of the three biomarkers using the same immunoassay batches in the three centers. RESULTS: In the three centers, tau (AUC, 0.82-0.88) and pTau-181 (AUC, 0.83-0.89) outperformed Aβ 1-42 (AUC, 0.70 -0.73) to discriminate subjects with AD from those without AD. An intersite variation of mean levels and cutoffs was observed for the three biomarkers. This variation was higher for Aβ 1-42 (range of cutoff, 368-582 pg/mL) than for tau (range of cutoff, 289-353 pg/mL). In a test-retest study, the mean interlaboratory coefficients of variation were 12.2% for Aβ 1-42, 11.3% for tau, and 11.5% for pTau-181. CONCLUSION: Intercenter variability of CSF biomarkers has been confirmed in a multisite cohort of subjects and can be improved in clinical settings. Efforts on harmonization of procedures should be encouraged to optimize the accuracy of CSF biomarkers in AD.
BACKGROUND: The assessment of total tau, phosphorylated tau (pTau-181) and amyloid beta (Aβ 1-42) concentrations in the cerebrospinal fluid (CSF) of subjects has been validated for the diagnosis of Alzheimer's disease (AD). Although these measurements have shown some variability, little is known about their intersite variability in clinical settings. METHODS: A total of 880 subjects (AD, n = 515; non-AD, n = 365) from three French memory centers were included. Receiver-operating characteristic analyses were performed to computerized area under curves (AUCs) and optimal thresholds for each biomarker in the three centers. A test-retest study was performed in a group of 32 CSF samples by repeated blind analysis of the three biomarkers using the same immunoassay batches in the three centers. RESULTS: In the three centers, tau (AUC, 0.82-0.88) and pTau-181 (AUC, 0.83-0.89) outperformed Aβ 1-42 (AUC, 0.70 -0.73) to discriminate subjects with AD from those without AD. An intersite variation of mean levels and cutoffs was observed for the three biomarkers. This variation was higher for Aβ 1-42 (range of cutoff, 368-582 pg/mL) than for tau (range of cutoff, 289-353 pg/mL). In a test-retest study, the mean interlaboratory coefficients of variation were 12.2% for Aβ 1-42, 11.3% for tau, and 11.5% for pTau-181. CONCLUSION: Intercenter variability of CSF biomarkers has been confirmed in a multisite cohort of subjects and can be improved in clinical settings. Efforts on harmonization of procedures should be encouraged to optimize the accuracy of CSF biomarkers in AD.
Authors: Fei Liu; Zhi-Qin Xue; Si-Hao Deng; Xiong Kun; Xue-Gang Luo; Peter R Patrylo; Gregory M Rose; Huaibin Cai; Robert G Struble; Yan Cai; Xiao-Xin Yan Journal: Eur J Neurosci Date: 2013-02-22 Impact factor: 3.386
Authors: Ge Li; Steven P Millard; Elaine R Peskind; Jing Zhang; Chang-En Yu; James B Leverenz; Cynthia Mayer; Jane S Shofer; Murray A Raskind; Joseph F Quinn; Douglas R Galasko; Thomas J Montine Journal: JAMA Neurol Date: 2014-06 Impact factor: 18.302
Authors: Catherine Pan; Ané Korff; Douglas Galasko; Carmen Ginghina; Elaine Peskind; Ge Li; Joseph Quinn; Thomas J Montine; Kevin Cain; Min Shi; Jing Zhang Journal: J Alzheimers Dis Date: 2015 Impact factor: 4.472
Authors: Yue Ma; Derek L Norton; Carol A Van Hulle; Richard J Chappell; Karen K Lazar; Erin M Jonaitis; Rebecca L Koscik; Lindsay R Clark; Rachel Krause; Ulf Andreasson; Nathaniel A Chin; Barbara B Bendlin; Sanjay Asthana; Ozioma C Okonkwo; Carey E Gleason; Sterling C Johnson; Henrik Zetterberg; Kaj Blennow; Cynthia M Carlsson Journal: Alzheimers Dement (Amst) Date: 2021-05-25