Monoclonal antibody with conformational specificity for a toxic conformer of amyloid ?42 and its application toward the Alzheimer's disease diagnosis.

ABSTRACT: Amyloid ?-protein (A?42) oligomerization is an early event in Alzheimer's disease (AD). Current diagnostic methods using sequence-specific antibodies against less toxic fibrillar and monomeric A?42 run the risk of overdiagnosis. Hence, conformation-specific antibodies against neurotoxic A?42 oligomers have garnered much attention for developing more accurate diagnostics. Antibody 24B3, highly specific for the toxic A?42 conformer that has a turn at Glu22 and Asp23, recognizes a putative A?42 dimer, which forms stable and neurotoxic oligomers more potently than the monomer. 24B3 significantly rescues A?42-induced neurotoxicity, whereas sequence-specific antibodies such as 4G8 and 82E1, which recognizes the N-terminus, do not. The ratio of toxic to total A?42 in the cerebrospinal fluid of AD patients is significantly higher than in control subjects as measured by sandwich ELISA using antibodies 24B3 and 82E1. Thus, 24B3 may be useful for AD diagnosis and therapy.

SUBMITTER: Murakami K 

PROVIDER: S-EPMC4931470 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature