Affiliations: [a] Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA | [b] Avid Radiopharmaceuticals, Inc., Philadelphia, PA, USA
Correspondence:
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Correspondence to: Li-San Wang, 1424 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA. Tel.: +1 215 746 7015; Fax: +1 215 573 3111; E-mail: lswang@mail.med.upenn.edu.
Note: [1] Deceased.
Abstract: The best-studied biomarkers of Alzheimer's disease (AD) are the pathologically-linked cerebrospinal fluid (CSF) proteins amyloid-β 42 (Aβ1-42), total tau (t-tau), and tau phosphorylated on amino acid 181 (p-tau181). Many laboratories measure these proteins using enzyme-linked immunosorbent assay (ELISA). Multiplex xMAP Luminex is a semi-automated assay platform with reduced intra-sample variance, which could facilitate its use in CLIA-approved clinical laboratories. CSF concentrations of these three biomarkers reported using xMAP technology differ from those measured by the most commonly used ELISA, confounding attempts to compare results. To develop a model for converting between xMAP and ELISA levels of the three biomarkers, we analyzed CSF samples from 140 subjects (59 AD, 30 controls, 34 with mild cognitive impairment, and 17 with Parkinson's disease, including 1 with dementia). Log-transformation of ELISA and xMAP levels made the variance constant in all three biomarkers and improved the linear regression: t-tau concentrations were highly correlated (r = 0.94); p-tau181 concentrations by ELISA can be better predicted using both the t-tau and p-tau181 xMAP values (r = 0.96) as compared to p-tau181 concentrations alone (r = 0.82); correlation of Aβ1-42 concentrations was relatively weaker but still high (r = 0.77). Among all six protein/assay combinations, xMAP Aβ1-42 had the best accuracy for diagnostic classification (88%) between AD and control subjects. In conclusion, our study demonstrates that multiplex xMAP is an appropriate assay platform providing results that can be correlated with research-based ELISA values, facilitating the incorporation of this diagnostic biomarker into routine clinical practice.
