FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease

Overview

Journal Anal Chem

Specialty Chemistry

Date 2016 Feb 16

PMID 26877193

Citations 73

Authors

Waltraud Mair

Jan Muntel

Katharina Tepper

Shaojun Tang

Jacek Biernat

William W Seeley

Kenneth S Kosik

Eckhard Mandelkow

Hanno Steen

Judith A Steen

Affiliations

Soon will be listed here.

Abstract

Tauopathies, including Alzheimer's disease (AD), are associated with the aggregation of modified microtubule associated protein tau. This pathological state of tau is often referred to as "hyperphosphorylated". Due to limitations in technology, an accurate quantitative description of this state is lacking. Here, a mass spectrometry-based assay, FLEXITau, is presented to measure phosphorylation stoichiometry and provide an unbiased quantitative view of the tau post-translational modification (PTM) landscape. The power of this assay is demonstrated by measuring the state of hyperphosphorylation from tau in a cellular model for AD pathology, mapping, and calculating site occupancies for over 20 phosphorylations. We further employ FLEXITau to define the tau PTM landscape present in AD post-mortem brain. As shown in this study, the application of this assay provides mechanistic understanding of tau pathology that could lead to novel therapeutics, and we envision its further use in prognostic and diagnostic approaches for tauopathies.

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