Tau Kinetics in Neurons and the Human Central Nervous System

Chihiro Sato, Nicolas R. Barthélemy, 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

Research output: Contribution to journalArticle

84 Scopus citations

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. Sato et al. show that stable isotope labeling kinetics enable measurement of tau in the CNS and in iPSC-derived neurons. Specific forms of tau are uniquely processed in neurons and tau production rates correlate with amyloid accumulation in human subjects.

Original languageEnglish
Pages (from-to)1284-1298.e7
JournalNeuron
Volume97
Issue number6
DOIs
StatePublished - Mar 21 2018

Keywords

  • Alzheimer's disease
  • PET
  • SILK
  • amyloid
  • human
  • induced pluripotent stem cell
  • isoform
  • phosphorylation
  • positron emission tomography
  • production rate
  • stable isotope labeling kinetics
  • tau

Fingerprint Dive into the research topics of 'Tau Kinetics in Neurons and the Human Central Nervous System'. Together they form a unique fingerprint.

  • Cite this

    Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., Kanaan, N. M., Yarasheski, K. E., Baker-Nigh, A., Benzinger, T. L. S., Miller, T. M., Karch, C. M., & Bateman, R. J. (2018). Tau Kinetics in Neurons and the Human Central Nervous System. Neuron, 97(6), 1284-1298.e7. https://doi.org/10.1016/j.neuron.2018.02.015