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

Abstract

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‐tau₁₉₉) by a recently established sandwich ELISA. The CSF/phospho‐tau₁₉₉ 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 versus all the other non‐AD groups using the CSF/phospho‐tau₁₉₉ were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho‐tau₁₉₉ and CSF/total‐tau levels in the AD group. Elevated CSF/phospho‐tau₁₉₉ in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho‐tau₁₉₉ may be a novel and logical biomarker in supporting antemortem diagnosis of AD.