Tau Phosphorylation Assays

Tau Phosphoprotein Assays for Tauopathies & Alzheimer’s Disease

Measure multiple phospho-Tau sites simultaneously
 
Tangles of Tau protein are characteristic of the damaged brain tissues of patients suffering from a variety of neurogenerative diseases known collectively as Tauopathies. The most common of these is Alzheimer’s Disease (AD), and whist the exact function and role Tau plays in AD etiology is not yet fully understood, assays for measurement of Tau remain a key tool for monitoring disease progression. One well understood role for Tau protein in normal healthy brain tissue is its structural role in stabilizing the scaffold of the cell through binding to microtubules, which is mediated by the phosphorylation state of Tau. Hyper-phosphorylation of Tau causes release of Tau from microtubules and is typical in AD tissue and been shown to correlate with Tau aggregation and formation of tangles. More recently, altered distribution of phosphorylated Tau has been shown to disrupt synaptic transmission, leading to loss of synapses in human hippocampus. Consequently, any effective treatment for AD is likely to require active reversal of Tau phosphorylation, and methods to assess levels of phosphorylation are therefore urgently required.


Proteome Sciences offers a range of different assays for measurement of phospho-Tau variants in different sample types. 

Applications Sample Types Species Analysis Method
Drug discovery from Tauopathies, Alzheimer's & Parkinson's diseases

Mouse brain, Tissue culture cells, CSF 

 Mouse, Human  AQUA-SRM Mass Spectrometry
*Clinical Analysis; early disease detection/prognostic

*CSF, Blood cells

 Human AQUA Mass Spectrometry 

* In Development

Assays for basic research and pre-clinical drug development

Proteome Sciences offers unique phospho-Tau biomarker panels for simultaneous mass spectrometry measurement of total Tau protein and 6 specific phosphorylation sites that have been strongly linked with Tau pathology. Both human and murine Tau isoforms may be analyzed from either transgenic murine brain tissue or human and murine cultured cells. The assay is available in 2 versions to enable measurement of phospho-Tau for different Tau transgene variants.

  • Tau Phosphorylation 6-plex – Most commonly used Tau transgenic variants
  • Tau R406W Phosphorylation 7-plex – use with mutant Tau R406W transgene 

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Tau Phosphorylation Biomarker Assays offer:

  • Measurement of phospho- and total Tau in murine brain or in human and murine cultured cells
  • Off-the-shelf Mass Spectrometry assay service available through ISO 9001:2008 accredited facility
  • Unique proprietary panel of phospho-Tau biomarkers
  • Measure specific phospho-Tau sites for which antibody detection is not possible
  • Accurate, precise and reproducible results
  • HPLC sample fractionation for highest degree of purity & sensitivity
  • Proven ability to monitor Tau kinase inhibitor activity in cell culture (see table below)


Assays for clinical research and patient diagnosis/prognosis

There is currently no reliable and definitive approved diagnostic test for Alzheimer’s Disease. However, measurement of amyloid beta and phosphorylated Tau in patient Cerebrospinal Fluid (CSF) samples is recognized as the best available test at present. Current immunoassay tests are limited to measuring only one phosphorylation site in Tau at a time. We believe a more comprehensive survey of Tau phosphorylation in CSF will provide better clinical understanding and so we are adapting our assays to enable measurement of multiple Tau proteins in CSF samples in a single method.

Tau Phosphorylation CSF 6-plex Assay will offer:

  • Accurate measurement of phospho- and total Tau in human CSF
  • Aids clinical diagnosis of Alzheimer’s
  • Prognosis of disease severity and progression
  • Patient stratification for clinical trials
  • Monitor patient response to therapy
  • Off-the-shelf Mass Spectrometry assay service available through ISO 9001:2008 accredited facility

Tau Phosphorylation 6-plex 

 Tau R406W Phosphorylation 7-plex
 Human   Associated Kinases Murine  Human   Associated Kinases  Murine
 Total Tau    Total Tau  Total Tau    Total Tau
 pTau (Thr181) GSK3b   pTau (Thr170)  pTau (Ser46)  CK1d, GSK3b  Not Included
 pTau (Ser199)  CK2, GSK3b, PKA  pTau (Ser188)  pTau (Thr50)  CK1d, GSK3b  No Murine Equivalent
 pTau (Thr231)  GSK3b, PKA  pTau (Thr220)  pTau (Ser113)*  CK1d  No Murine Equivalent
 pTau (Ser262)  CK1d, GSK3b, PKA  pTau (Ser251)  pTau (Ser396)  CK1d, CK2, GSK3b  pTau (Ser385)
 pTau (Ser396)  CK1d, CK2, GSK3b  p-Tau (Ser385)  pTau (Ser404)  CK1d, CK2, GSK3b  pTau (Ser393)
       pTau (Ser433)*  CK1d  pTau (Ser422)

 N.B. *CK1d unique site; phospho-site numbering based on human 2N4R tau.

 
  
 To Download Tau Phosphorylation Biomarker Assay Product Brochure Click Here