Immuno-PCR-based quantification of multiple phosphorylated tau-epitopes linked to Alzheimer's disease

Anal Bioanal Chem. 2009 Dec;395(7):2263-7. doi: 10.1007/s00216-009-3208-8. Epub 2009 Oct 11.


Several lines of evidence suggest that quantification of phosphorylated sites in the tau-protein (phospho-tau) might be favorable for early and specific Alzheimer's disease diagnosis. The typical setup to quantify phosphorylated tau-epitopes relies on a sandwich ELISA with a capture antibody (Ab) recognizing tau independent of its phosphorylation status and a detector Ab binding specifically to a certain phosphorylation site. Besides Ab specificities, major challenges arise from the very low tau-concentrations in cerebrospinal fluid (CSF) ranging from 100 to 2,000 pg/ml. Based on the phosphorylation degree of a given position, which can be below 10%, the corresponding phospho-tau-level might be much lower, especially for multiphosphorylated epitopes studied here. Thus, a novel, highly sensitive, and generally applicable immunoassay is described to quantify tau-versions, which are phosphorylated at pThr212/pSer214/pThr231/pSer235, down to tau-concentrations of 2 pg/ml in CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / metabolism*
  • Antibodies
  • Biomarkers
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes
  • Humans
  • Phosphorylation
  • Polymerase Chain Reaction / methods*
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism*


  • Antibodies
  • Biomarkers
  • Epitopes
  • tau Proteins