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

Hyperphosphorylation of the microtubule-associated protein tau is specifica lly found in those brain cells affected in several tauopathies. Tau has als o been consistently found to be present in the cerebrospinal fluid (CSF). H ere we report the quantification in CSF of tau phosphorylated at Thr 181 us ing an immunoassay with a synthetic peptide for standardization. The choice of the peptide was based on fine mapping of a phospho-dependent antibody, AT270 (P(176)PAPKT(p)-P-132). and a human specific tau antibody, HT7 (P(159 )PGQK(163)) 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, r(2) = 0. 73; frontotemporal dementia, r(2) = 0.43; Control, r(2) = 0.42), suggesting that the degree of phosphorylation of CSF-tau changes in different clinica l conditions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.