Characterization of murine immunoglobulin G antibodies against human amyloid-β1-42

It has been demonstrated that immunization of transgenic mouse models of Alzheimer's disease (AD) with amyloid-beta (1-42) peptide (A beta (1-42)) results in amelioration of AD-like pathology, including reduced soluble and deposited beta -amyloid and decreased cognitive impairment. Based on the proposed importance of immunoglobulin G (IgG) anti-A beta antibodies (Abs) in these effects, we sought to characterize these Abs in splenocytes from mice immunized with A beta (1-42) Data show that a more aggregated preparation of A beta (1-42) gives a robust IgG anti-A beta Ab response, while these Abs are almost undetectable when a less aggregated preparation of A beta (1-42) is used as the immunogen. importantly, IgG anti-A beta Ab production is detected after just 12 weeks of A beta (1-42) treatment. Analysis of anti-A beta Ab IgG isotypes reveals that the majority of these Abs are IgG1, with significantly fewer Abs of the IgG2a or IgG2b isotypes (IgG1 > IgG2a > IgG2b), suggesting a T lymphocyte helper type ii response after A beta (1-42) immunization. To determine the epitope of AP recognized by IgG anti-A beta Abs, intact A beta and A beta peptide fragments were analyzed for their ability to bind these Abs. Data show that these Abs specifically recognize an amino-terminal epitope of A beta between amino acids one and twelve, with higher affinity for a more soluble preparation of A beta (1-42) These data further indicate the immunogenic potential of A beta (1-42) and offer insight into the nature of the IgG anti-A beta Ab response. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.