TOC1: Characterization of a Selective Oligomeric Tau Antibody

The work presented herein addresses a specific portion of the tau pathology, pre-fibrillar oligomers, now thought to be important pathological components in Alzheimer's disease and other neurodegenerative tauopathies. In previous work, we generated an antibody against purified recombinant cross-linked tau dimers, called Tau Oligomeric Complex 1 (TOC1). TOC1 recognizes tau oligomers and its immunoreactivity is elevated in Alzheimer's disease brains. In this report, we expand upon the previous study to show that TOC1 selectively labels tau oligomers over monomers or polymers, and that TOC1 is also reactive in other neurodegenerative tauopathies. Using a series of deletion mutants spanning the tau molecule, we further demonstrate that TOC1 has one continuous epitope located within amino acids 209-224, in the so-called proline rich region. Together with the previous study, our data indicates that TOC1 is a conformation-dependent antibody whose epitope is revealed upon dimerization and oligomerization, but concealed again as polymers form. This characterization of the TOC1 antibody further supports its potential as a powerful biochemical tool that can be used to better investigate the involvement of tau in neurodegenerative diseases.