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Publication

Tau Kinetics in Neurons and the Human Central Nervous System.

Neuron | 2018

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.

Pubmed ID: 29566794 RIS Download

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Associated grants

Agency: NIA NIH HHS, United States
Id: K01 AG053474
Agency: NIA NIH HHS, United States
Id: P01 AG003991
Agency: NIA NIH HHS, United States
Id: P50 AG005681
Agency: NIDDK NIH HHS, United States
Id: P30 DK056341
Agency: NIA NIH HHS, United States
Id: P01 AG026276
Agency: NIGMS NIH HHS, United States
Id: P41 GM103422
Agency: NINDS NIH HHS, United States
Id: P30 NS098577
Agency: NIA NIH HHS, United States
Id: K01 AG046374
Agency: NINDS NIH HHS, United States
Id: R01 NS078398
Agency: NINDS NIH HHS, United States
Id: P30 NS048056
Agency: NCATS NIH HHS, United States
Id: UL1 TR000448
Agency: NINDS NIH HHS, United States
Id: R01 NS095773
Agency: NIDDK NIH HHS, United States
Id: P30 DK020579
Agency: NCATS NIH HHS, United States
Id: UL1 TR002345

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