Mechanisms of recognition of amyloid-β (Aβ) monomer, oligomer, and fibril by homologous antibodies.

ABSTRACT: Alzheimer's disease is one of the most devastating neurodegenerative diseases without effective therapies. Immunotherapy is a promising approach, but amyloid antibody structural information is limited. Here we simulate the recognition of monomeric, oligomeric, and fibril amyloid-β (Aβ) by three homologous antibodies (solanezumab, crenezumab, and their chimera, CreneFab). Solanezumab only binds the monomer, whereas crenezumab and CreneFab can recognize different oligomerization states; however, the structural basis for this observation is not understood. We successfully identified stable complexes of crenezumab with Aβ pentamer (oligomer model) and 16-mer (fibril model). It is noteworthy that solanezumab targets Aβ residues 16-26 preferentially in the monomeric state; conversely, crenezumab

SUBMITTER: Zhao J 

PROVIDER: S-EPMC5672054 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature