Structural and functional analyses of pyroglutamate-amyloid-β-specific antibodies as a basis for Alzheimer immunotherapy.

ABSTRACT: Alzheimer disease is associated with deposition of the amyloidogenic peptide Aβ in the brain. Passive immunization using Aβ-specific antibodies has been demonstrated to reduce amyloid deposition both in vitro and in vivo Because N-terminally truncated pyroglutamate (pE)-modified Aβ species (Aβ_pE3) exhibit enhanced aggregation potential and propensity to form toxic oligomers, they represent particularly attractive targets for antibody therapy. Here we present three separate monoclonal antibodies that specifically recognize Aβ_pE3 with affinities of 1-10 nm and inhibit Aβ_pE3 fibril formation in vitro. In vivo application of one of these resulted in improved memory in Aβ_pE3 oligomer-treated mice. Crystal structures of F_ab

SUBMITTER: Piechotta A 

PROVIDER: S-EPMC5535044 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature