Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome

Mol Neurodegener. 2017 Sep 4;12(1):63. doi: 10.1186/s13024-017-0206-8.


Background: There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD.

Methods: We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts.

Results: In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R2 = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R2 = 0.4525, p = 0.023).

Conclusions: We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.

Keywords: Alzheimer’s disease; Down syndrome; Plasma biomarker; Simoa; Tau phosphorylated at threonine 181 (p-tau181).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / blood
  • Biomarkers / blood*
  • Brain / metabolism*
  • Case-Control Studies
  • Down Syndrome / blood
  • Down Syndrome / diagnosis*
  • Down Syndrome / pathology
  • Female
  • Humans
  • Male
  • Phosphorylation
  • Pilot Projects
  • tau Proteins / blood*


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins