Comparison of xMAP and ELISA assays for detecting cerebrospinal fluid biomarkers of Alzheimer's disease

Abstract

The best-studied biomarkers of Alzheimer's disease (AD) are the pathologically-linked cerebrospinal fluid (CSF) proteins amyloid-β 42 (Aβ(1-42)), total tau (t-tau), and tau phosphorylated on amino acid 181 (p-tau(181)). 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-tau(181) concentrations by ELISA can be better predicted using both the t-tau and p-tau(181) xMAP values (r = 0.96) as compared to p-tau(181) concentrations alone (r = 0.82); correlation of Aβ(1-42) concentrations was relatively weaker but still high (r = 0.77). Among all six protein/assay combinations, xMAP Aβ(1-42) 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.

Figure 1

Scatter plot of ELISA t-tau measurements and corresponding estimated levels by xMAP regression model.

Figure 2

Scatter plot of ELISA p-tau₁₈₁ measurements and corresponding estimated levels by xMAP regression model.

Figure 3

Scatter plot of ELISA Aβ_1–42 measurements and corresponding estimated levels by xMAP regression model.

Figure 4

Scatter plot of xMAP t-tau measurements and corresponding estimated levels by ELISA regression model.

Figure 5

Scatter plot of xMAP p-tau₁₈₁ measurements and corresponding estimated levels by ELISA regression model.

Figure 6

Scatter plot of xMAP Aβ_1–42 measurements and corresponding estimated levels by ELISA regression model.