Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease

We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n. = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho-tau(199)) by a recently established sandwich ELISA. The CSF/phospho-tau(199) levels in the AD group were significantly elevated compared to those in all the other non-AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group vs all the other non-AD groups using the CSF/phospho-tau(199) were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho-tau(199) and CSF/total-tau levels in the AD group. Elevated CSF/phospho-tau(199) in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho-tan(199) may be a novel and logical biomarker in supporting antemortem diagnosis of AD.