Anti-tau antibodies targeting a conformation-dependent epitope selectively bind seeds.

ABSTRACT: Neurodegenerative tauopathies are caused by the transition of tau protein from a monomer to a toxic aggregate. They include Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease (PiD). We have previously proposed that tau monomer exists in two conformational ensembles: an inert form (M_i), which does not self-assemble, and seed-competent form (M_s), which self-assembles and templates ordered assembly growth. We proposed that cis/trans isomerization of tau at P301, the site of dominant disease-associated S/L missense mutations, might underlie the transition of wild-type tau to a seed-competent state. Consequently, we created monoclonal antibodies using non-natural antigens consisting of fluorinated proline (P∗) at

SUBMITTER: Hitt BD 

PROVIDER: S-EPMC10582770 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature