Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization

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Abstract

Hyperphosphorylation of the microtubule-associated protein tau is specifically found in those brain cells affected in several tauopathies. Tau has also been consistently found to be present in the cerebrospinal fluid (CSF). Here we report the quantification in CSF of tau phosphorylated at Thr 181 using an immunoassay with a synthetic peptide for standardization. The choice of the peptide was based on fine mapping of a phospho-dependent antibody, AT270 (P176PAPKTpP132)and a human specific tau antibody, HT7 (P159PGQK163). CSF-phospho-tau levels were increased in Alzheimer patients (23.5±10.1 pM, P<0.01) compared with age-matched controls (15.9±5.7 pM), while decreased in patients with frontotemporal dementia (8.6±3.9 pM; P<0.01). In every diagnostic group, a highly significant correlation was found between total tau and phospho-tau (Alzheimer's disease, r2=0.73; frontotemporal dementia, r2=0.43; Control, r2=0.42), suggesting that the degree of phosphorylation of CSF-tau changes in different clinical conditions.

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Acknowledgements

This work was supported by a grant from the ‘Vlaams Instituut voor de bevordering van het Wetenschappelijk Technologisch onderzoek in de industrie’ (Grant 990220) and the Medical Research Council, Sweden, Grant No. 12103 and 11560. Fred Shapiro is thanked for critical review and editing of the manuscript and Bob DeLeys for the initial experiments on the epitope mapping.

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