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P1–183: Identification of an important potential confound in CSF Alzheimer's disease studies: Aliquot volume
Author(s) -
Paterson Ross,
Toombs Jamie,
Fox Nick,
Nicholas Jennifer,
Miles Chapman,
Schott Jonathan,
Zetterberg Henrik
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.406
Subject(s) - biomarker , confounding , volume (thermodynamics) , chemistry , medicine , chromatography , biochemistry , physics , quantum mechanics
shows excellent correlation and lack of bias (mean bias 1⁄4 1.3% [range 1⁄4 -11.2 +12.1%]) between aCSF -based vs. human CSF-based calibration. These results provide further substantiation for equivalence of aCSF as a calibrator matrix compared to human CSF-based calibration. ROC analyses of the autopsy-confirmed AD cases versus the NC group: AUC, diagnostic sensitivity, specificity, positive, negative predictive values, and diagnostic test efficiency were, respectively: 0.94, 92.7%, 85.4%, 86.4%, 92.1% and 89%. For the AlzBio3 immunoassay, respective values were: 0.90, 100%, 78%, 82%, 100% and 89%. The two methods were significantly correlated (p<0.0001; r 2 1⁄4 0.67) and SRM/tandem/MSMS concentrations were approximately 4 times higher than AlzBio3.Conclusions: This study provides for the first time qualification data supporting use of a surrogate calibration matrix-based 2D/UPLC/SRM/tandem/MSMS method for accurate and precise quantification of A b 1-42 in human CSF. Another important result of this work is the demonstration of nearly equivalent clinical performance to that obtained by the AlzBio3 immunoassay in 41 subjects with pathologically based AD diagnosis compared to normal subjects.