Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers

The deposition of highly phosphorylated and aggregated tau is a characteristic of tauopathies, including Alzheimer's disease. It has long been known that different isoforms of tau are aggregated in different cell types and brain regions in each tauopathy. Recent advances in analytical technique...

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Main Authors: Taeko Kimura, Haruaki Sato, Maria Kano, Lisa Tatsumi, Taisuke Tomita
Format: Article
Language:English
Published: Wiley 2024-02-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13667
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author Taeko Kimura
Haruaki Sato
Maria Kano
Lisa Tatsumi
Taisuke Tomita
author_facet Taeko Kimura
Haruaki Sato
Maria Kano
Lisa Tatsumi
Taisuke Tomita
author_sort Taeko Kimura
collection DOAJ
description The deposition of highly phosphorylated and aggregated tau is a characteristic of tauopathies, including Alzheimer's disease. It has long been known that different isoforms of tau are aggregated in different cell types and brain regions in each tauopathy. Recent advances in analytical techniques revealed the details of the biochemical and structural biological differences of tau specific to each tauopathy. In this review, we explain recent advances in the analysis of post‐translational modifications of tau, particularly phosphorylation, brought about by the development of mass‐spectrometry and Phos‐tag technology. We then discuss the structure of tau filaments in each tauopathy revealed by the advent of cryo‐EM. Finally, we describe the progress in biofluid and imaging biomarkers for tauopathy. This review summarizes current efforts to elucidate the characteristics of pathological tau and the landscape of the use of tau as a biomarker to diagnose and determine the pathological stage of tauopathy.
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spelling doaj.art-c0e9e5e63afc43189335879b673e1ac02024-02-05T06:39:38ZengWileyFEBS Open Bio2211-54632024-02-0114218119310.1002/2211-5463.13667Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkersTaeko Kimura0Haruaki Sato1Maria Kano2Lisa Tatsumi3Taisuke Tomita4Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences The University of Tokyo JapanLaboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences The University of Tokyo JapanLaboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences The University of Tokyo JapanLaboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences The University of Tokyo JapanLaboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences The University of Tokyo JapanThe deposition of highly phosphorylated and aggregated tau is a characteristic of tauopathies, including Alzheimer's disease. It has long been known that different isoforms of tau are aggregated in different cell types and brain regions in each tauopathy. Recent advances in analytical techniques revealed the details of the biochemical and structural biological differences of tau specific to each tauopathy. In this review, we explain recent advances in the analysis of post‐translational modifications of tau, particularly phosphorylation, brought about by the development of mass‐spectrometry and Phos‐tag technology. We then discuss the structure of tau filaments in each tauopathy revealed by the advent of cryo‐EM. Finally, we describe the progress in biofluid and imaging biomarkers for tauopathy. This review summarizes current efforts to elucidate the characteristics of pathological tau and the landscape of the use of tau as a biomarker to diagnose and determine the pathological stage of tauopathy.https://doi.org/10.1002/2211-5463.13667Alzheimer's diseaseblood biomarkercryo‐EMphosphorylationtau PETtauopathy
spellingShingle Taeko Kimura
Haruaki Sato
Maria Kano
Lisa Tatsumi
Taisuke Tomita
Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
FEBS Open Bio
Alzheimer's disease
blood biomarker
cryo‐EM
phosphorylation
tau PET
tauopathy
title Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
title_full Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
title_fullStr Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
title_full_unstemmed Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
title_short Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers
title_sort novel aspects of the phosphorylation and structure of pathological tau implications for tauopathy biomarkers
topic Alzheimer's disease
blood biomarker
cryo‐EM
phosphorylation
tau PET
tauopathy
url https://doi.org/10.1002/2211-5463.13667
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