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Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model.
Manos, Justine D; Preiss, Christina N; Venkat, Nandini; Tamm, Joseph; Reinhardt, Peter; Kwon, Taekyung; Wu, Jessica; Winter, Allison D; Jahn, Thomas R; Yanamandra, Kiran; Titterton, Katherine; Karran, Eric; Langlois, Xavier.
Afiliación
  • Manos JD; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Preiss CN; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Venkat N; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Tamm J; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Reinhardt P; AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, Knollstrasse, 67061 Ludwigshafen, Germany.
  • Kwon T; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Wu J; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Winter AD; Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
  • Jahn TR; AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, Knollstrasse, 67061 Ludwigshafen, Germany.
  • Yanamandra K; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Titterton K; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Karran E; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
  • Langlois X; Abbvie, Cambridge Research Center, 200 Sidney Street, Cambridge, MA 02139, USA.
iScience ; 25(1): 103658, 2022 Jan 21.
Article en En | MEDLINE | ID: mdl-35072001
Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal in vitro models have struggled to recapitulate tau phenomena observed in vivo. Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates. Importantly, MAPT-wild type and MAPT-mutant hiPSC-neurons exhibited unique propensities for aggregation dependent on the seed strain rather than the repeat domain identity, suggesting that successful templating of the recipient tau may be driven by the unique conformation of the seed. The in vitro model presented here represents the first successful demonstration of combining human neurons, endogenous tau expression, and AD brain-derived competent tau species, offering a more physiologically relevant platform to study tau pathobiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
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