Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer's Disease and Mild Cognitive Impairment Patients.

Shashank Shekhar,Ashish Datt Upadhyay,Rahul Kumar,Nitish Rai,Kusum Singh,Manjari Tripathi,Sadanand Dwivedi,Sharmistha Dey,Vijay Kumar,Aparajit B Dey,Pradeep Garg

doi:10.1371/journal.pone.0159099

Abstract

The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer’s disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/μL, p-Tau181; 0.161±0.04 ng/μL) compared to MCI (Tau; 39.26±7.78 ng/μL, p-Tau181; 0.135±0.02 ng/μL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/μL, p-Tau181; 0.122±0.01 ng/ μL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI.

Highlights

Alzheimer’s disease (AD) is neurodegenerative disorder which causes a progressive dementia that currently affects over 35.6 million individuals worldwide and it is expected that it will be more than triple by 2050[1]
Analysis of covariance was applied and adjusted mean, standard error (SE) and pvalue was reported after adjusting gender and education between three groups (Table 2)
The concept of blood based biomarkers for AD is alluring, and these could be put to many uses, such as screening, diagnosis, risk assessment, and as an aid to drug development in clinical trials

Summary

Introduction

Alzheimer’s disease (AD) is neurodegenerative disorder which causes a progressive dementia that currently affects over 35.6 million individuals worldwide and it is expected that it will be more than triple by 2050[1]. While the numbers are likely to be double by 2030, and cost would increase three times [2]. This imitates the socioeconomic burden of AD. There is no cure or disease-modifying therapies, and this may be due to our incapability to diagnose the disease before it has progressed to produce evident memory loss and functional decline.The biomarkers of disease will be critical for the development of disease-modifying or even preventive therapies. The current available biomarkers for AD are either CSF based or imaging based which is either invasive, time consuming or highly expensive [3]

Methods

Results

Conclusion