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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Veröffentlicht in:Neuron (Cambridge, Mass.) Jg. 97; H. 6; S. 1284
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 21.03.2018
Schlagworte:
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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Beschreibung
Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1097-4199
1097-4199
DOI:10.1016/j.neuron.2018.02.015