Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease

Neurosci Lett. 1999 Jul 30;270(2):91-4. doi: 10.1016/s0304-3940(99)00476-0.


Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Biomarkers / cerebrospinal fluid
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Reference Values
  • tau Proteins / cerebrospinal fluid*
  • tau Proteins / metabolism


  • Biomarkers
  • Peptide Fragments
  • tau Proteins