Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Morris JC, Holtzman DM.
Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology.
Arch Neurol. 2011 Sep;68(9):1137-44.
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This study is timely in comparing two widely used platforms (ELISA and bead-based multiplex assays [X-MAP]) for measuring cerebrospinal fluid (CSF) analytes related to Alzheimer’s disease. The results support assays for CSF Aβ42 and total tau as being reliable across platforms, although at present, precise cutoff levels need to be established by users. Measurement of CSF levels of phospho-tau181 showed greater variability between the platforms, for unclear reasons. A particular strength of the study was amyloid imaging on all participants, allowing comparison of cutoffs of CSF biomarkers with amyloid positive or negative scans. The study does not discuss why each platform reads out different concentrations of Aβ42, tau and p-tau181 in CSF, although levels of each of these analytes were correlated using different assays; the strength of correlation does not allow for a facile conversion of levels between platforms.
A different standardization problem—how to obtain consistent readouts (and low variation) within a laboratory when assays are run intermittently on different days (rather than in large batches)—is the subject of ongoing research and harmonization efforts spearheaded by Kaj Blennow and others.