CSF p-Tau levels in the prediction of Alzheimer's disease

Ramesh J L Kandimalla,Alka Kaushal,Nidhi Gupta,Deep Raj Sharma,Sudesh Prabhakar,Willayat Yousuf Wani,Kajal Jain,V K Grover,Kiran Dip Gill,Neerja Bhardwaj

doi:10.1242/bio.20135447

Ramesh J L Kandimalla, Alka Kaushal + Show 8 more

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https://doi.org/10.1242/bio.20135447

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Abstract

SummaryThe two hallmarks of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid plaques. Neurofibrillary tangles are formed due to the hyperphosphorylation of tau protein. There is an urgent need to develop a reliable biomarker for the diagnosis of AD. Cerebrospinal fluid (CSF) is surrounding the brain and reflects the major neuropathological features in the AD brain. Diagnosis, disease progression and drug actions rely on the AD biomarkers. Mainly CSF tau and phosphorylated tau (p-Tau) have been observed to serve the purpose for early AD. Keeping in view the early appearance of p-Tau in CSF, we analyzed p-Tau levels in 23 AD, 23 Non AD type dementia (NAD), 23 Neurological control (NC) and 23 Healthy control (HC) North Indian patients. The levels of p-Tau were found to be increased in AD patients (67.87±18.05 pg/ml, SEM 3.76) compared with NAD (47.55±7.85 pg/ml, SEM 1.64), NC (34.42±4.51 pg/ml, SEM 0.94) and HC (27.09±7.18 pg/ml, SEM 1.50). The resulting sensitivity for AD with NAD was 80.27% whereas with respect to the NAD, NC and HC was 85.40%. Therefore elevated levels of p-Tau in AD can be exploited as a predictive biomarker in North Indian AD patients.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a slowly progressive dementia and brain atrophy
In this study, we evaluated the clinical usefulness of phosphorylated tau (p-Tau) as a biological marker in the diagnosis of AD in comparison with Non-AD type (NAD) dementia, Neurological controls (NC) and healthy controls (HC) initially in 23 patients in each group in North Indian population
cerebrospinal fluid (CSF) concentration of p-Tau181 The CSF concentrations of p-Tau 181 in AD, Non AD type dementia (NAD), NC and Healthy control (HC) are presented in Table 1, which clearly depicts the increase in the concentration of p-Tau 181 in comparison with the NAD, NC and HC

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a slowly progressive dementia and brain atrophy. In the window period the disease process and continues but both patient and clinician remain ignorant (Kandimalla et al, 2011a; Kandimalla et al, 2011b). Based on the Alois Alzheimer observations, there are differences in the dyed brain fibrils of a patient afflicted with dementia compared with fibrils in a normal brain. In more than 80% of AD patients the most consistent finding protein is microtubule associated protein i.e. tau in cerebrospinal fluid (CSF) which has direct contact with brain, where the change/modification in the protein levels can be monitored biochemically (Lewczuk et al, 2004). In AD brain tau protein accumulates in the form of hyperphosphorylated form

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