First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model.

ABSTRACT:

Introduction

We have identified structural determinants on tau protein that are essential for pathological tau-tau interaction in Alzheimer's disease (AD). These regulatory domains, revealed by monoclonal antibody DC8E8, represent a novel target for tau-directed therapy. In order to validate this target, we have developed an active vaccine, AADvac1.

Methods

A tau peptide encompassing the epitope revealed by DC8E8 was selected for the development of an active vaccine targeting structural determinants on mis-disordered tau protein that are essential for pathological tau-tau interaction. The efficacy of the vaccine was tested in a transgenic rat model of human tauopathies. Toxicology and safety pharmacology studies were conducted under good laboratory practice conditions in mul

SUBMITTER: Kontsekova E 

PROVIDER: S-EPMC4255368 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature