Tau Kinetics in Neurons and the Human Central Nervous System

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 hu...

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Podrobná bibliografia
Vydané v:	Neuron (Cambridge, Mass.) Ročník 97; číslo 6; s. 1284
Hlavní autori:	Sato, Chihiro, Barthélemy, Nicolas R, Mawuenyega, Kwasi G, Patterson, Bruce W, Gordon, Brian A, Jockel-Balsarotti, Jennifer, Sullivan, Melissa, Crisp, Matthew J, Kasten, Tom, Kirmess, Kristopher M, Kanaan, Nicholas M, Yarasheski, Kevin E, Baker-Nigh, Alaina, Benzinger, Tammie L S, Miller, Timothy M, Karch, Celeste M, Bateman, Randall J
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 21.03.2018
Predmet:	Aged Aged, 80 and over Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - metabolism Alzheimer Disease - pathology Amino Acid Sequence Biomarkers - cerebrospinal fluid Brain - metabolism Brain - pathology Cell Line Cells, Cultured Central Nervous System - metabolism Central Nervous System - pathology Female Humans Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Kinetics Male Middle Aged tau Proteins - cerebrospinal fluid tau Proteins - metabolism SILK amyloid Alzheimer’s disease induced pluripotent stem cell stable isotope labeling kinetics production rate tau positron emission tomography human phosphorylation PET isoform
ISSN:	1097-4199, 1097-4199
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4199 1097-4199
DOI:	10.1016/j.neuron.2018.02.015