No correlation between CSF tau protein phosphorylated at threonine 181 with neocortical neurofibrillary pathology in Alzheimer's disease

Sir, We have shown recently that tau protein hyperphosphorylated at threonine 231 (P-tau231P) in cerebrospinal fluid (CSF), a major candidate marker of Alzheimer's disease (AD), correlates with neurofibrillary pathology in the brain of mostly severely demented AD patients (Buerger et al., 2006). In a clinical study, however, it had been reported earlier, that P-tau subtypes perform differently in the discrimination between mild to moderate AD and comparison groups (Hampel et al., 2004). Recently, Engelborghs and colleagues investigated correlations between CSF levels of P-tau phosphorylated at threonine 181 (P-tau181P), another widely used P-tau candidate marker, and Braak NFT and NP stages (Braak and Braak, 1991) and found no associations (Engelborghs et al., 2007). Therefore, we tested whether CSF P-tau181P correlates with neurofibrillary pathology in our previously studied population. Post-mortem assessed parameters were amount of neurofibrillary tangles (NFT), neuritic plaques (NP), neuropil threads (HP-tau load) and P-tau181P concentration in tissue homogenates measured within the brain of 26 AD patients. The study population, materials and methods as well as statistical analyses were identical to our recent report (Buerger et al., 2006). Levels of P-tau181P in CSF and brain homogenates were determined using a commercially available ELISA (Innotest-Phospho-Tau(181P), Innogenetics, Belgium). To compare tau deposits stained by antibodies against phosphorylated tau at threonine 231 and threonine 181 in the brain of AD patients, additional immunohistochemical staining on tissue samples obtained from temporal cortex of all patients included in the study was carried out. Three different tau antibodies were used: monoclonal PHF-TAU clone AT8 (Innogenetics BR-03) that recognizes PHF-tau and the epitope has been shown to contain serine 202; PHF-TAU clone AT180 (Innogenetics BR-07) that recognizes PHF-tau and the epitope has been determined as being threonine 231; and PHF-TAU clone AT270 (Innogenetics BR-08) that recognizes PHF-tau and the epitope has been determined as being threonine 181. All antibodies were used in dilution of 1/500 and the staining was carried out without pretreatments with incubation overnight. Immunoreactivity was estimated semiquantitatively as mild, moderate or severe.