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Open Access 01-12-2017 | Research article

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

Authors: Harutsugu Tatebe, Takashi Kasai, Takuma Ohmichi, Yusuke Kishi, Tomoshi Kakeya, Masaaki Waragai, Masaki Kondo, David Allsop, Takahiko Tokuda

Published in: Molecular Neurodegeneration | Issue 1/2017

Abstract

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.

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Title: 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
Authors: Harutsugu Tatebe
Takashi Kasai
Takuma Ohmichi
Yusuke Kishi
Tomoshi Kakeya
Masaaki Waragai
Masaki Kondo
David Allsop
Takahiko Tokuda
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-017-0206-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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