Characterization of TauC3 antibody and demonstration of its potential to block tau propagation

PloS One
Samantha B NichollsBradley T Hyman

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.

References

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Citations

May 10, 2018·Frontiers in Neuroscience·Sarah L DeVosBradley T Hyman
Jul 10, 2018·Journal of Molecular Neuroscience : MN·Shweta Kishor Sonawane, Subashchandrabose Chinnathambi
Feb 14, 2021·Journal of Alzheimer's Disease : JAD·Wim Hendricus QuintThomas Vogels
May 13, 2018·Current Opinion in Neurobiology·Tara E Tracy, Li Gan
Jul 13, 2021·Frontiers in Molecular Neuroscience·Xiaomin YinWei Qian
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Huiqin ZhangHao Li

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Methods Mentioned

BETA
ELISA
surface plasmon resonance
chip
immunodepletion
electrophoresis
FRET
biosensor

Software Mentioned

Graphpad Prism
Image J

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