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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439699/
https://www.ncbi.nlm.nih.gov/pubmed/28531180
http://dx.doi.org/10.1371/journal.pone.0177914
Descripción
Sumario: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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