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

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2017

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Public Library of Science
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Nicholls, S. B., S. L. DeVos, C. Commins, C. Nobuhara, R. E. Bennett, D. L. Corjuc, E. Maury, et al. 2017. “Characterization of TauC3 antibody and demonstration of its potential to block tau propagation.” PLoS ONE 12 (5): e0177914. doi:10.1371/journal.pone.0177914. http://dx.doi.org/10.1371/journal.pone.0177914.

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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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Medicine and Health Sciences, Mental Health and Psychiatry, Dementia, Alzheimer Disease, Neurology, Neurodegenerative Diseases, Spectrum Analysis Techniques, Spectrophotometry, Fluorophotometry, Fluorescence Resonance Energy Transfer, Biology and Life Sciences, Biochemistry, Proteins, Recombinant Proteins, Brain Diseases, Cytoskeletal Proteins, Microtubule-Associated Proteins, Tau Protein, Precipitation Techniques, Immunoprecipitation, Health Care, Immunologic Techniques, Immunoassays, Enzyme-Linked Immunoassays

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