Tau Kinetics in Neurons and the Human Central Nervous System

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2018 Mar 24

PMID 29566794

Citations 242

Authors

Chihiro Sato

Nicolas R Barthelemy

Kwasi G Mawuenyega

Bruce W Patterson

Brian A Gordon

Jennifer Jockel-Balsarotti

Melissa Sullivan

Matthew J Crisp

Tom Kasten

Kristopher M Kirmess

Nicholas M Kanaan

Kevin E Yarasheski

Alaina Baker-Nigh

Tammie L S Benzinger

Timothy M Miller

Celeste M Karch

Randall J Bateman

Affiliations

Soon will be listed here.

Abstract

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology.

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