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Characterization of TauC3 antibody and demonstration of its potential to block tau propagation.
Nicholls, Samantha B; DeVos, Sarah L; Commins, Caitlin; Nobuhara, Chloe; Bennett, Rachel E; Corjuc, Diana L; Maury, Eduardo; Eftekharzadeh, Bahareh; Akingbade, Ololade; Fan, Zhanyun; Roe, Allyson D; Takeda, Shuko; Wegmann, Susanne; Hyman, Bradley T.
Affiliation
  • Nicholls SB; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • DeVos SL; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Commins C; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Nobuhara C; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Bennett RE; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Corjuc DL; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Maury E; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Eftekharzadeh B; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Akingbade O; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Fan Z; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Roe AD; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Takeda S; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Wegmann S; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
  • Hyman BT; Massachusetts General Hospital, Harvard Medical School, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts, United States of America.
PLoS One ; 12(5): e0177914, 2017.
Article in En | MEDLINE | ID: mdl-28531180
ABSTRACT
The spread of neurofibrillary tangle (NFT) pathology through the human brain is a hallmark of Alzheimer's disease (AD), which is thought to be caused by the propagation of "seeding" competent soluble misfolded tau. "TauC3", a C-terminally truncated form of tau that is generated by caspase-3 cleavage at D421, has previously been observed in NFTs and has been implicated in tau toxicity. Here we show that TauC3 is found in the seeding competent high molecular weight (HMW) protein fraction of human AD brain. Using a specific TauC3 antibody, we were able to substantially block the HMW tau seeding activity of human AD brain extracts in an in vitro tau seeding FRET assay. We propose that TauC3 could contribute to the templated tau misfolding that leads to NFT spread in AD brains.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Tau Proteins / Alzheimer Disease / Antibodies Limits: Aged80 / Female / Humans / Male / Middle aged Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2017 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Tau Proteins / Alzheimer Disease / Antibodies Limits: Aged80 / Female / Humans / Male / Middle aged Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2017 Document type: Article Affiliation country: United States