Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42.

Abstract:

:It has been demonstrated that immunization of transgenic mouse models of Alzheimer's disease (AD) with amyloid-beta1-42 peptide (Abeta1-42) 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-Abeta antibodies (Abs) in these effects, we sought to characterize these Abs in splenocytes from mice immunized with Abeta1-42. Data show that a more aggregated preparation of Abeta1-42 gives a robust IgG anti-Abeta Ab response, while these Abs are almost undetectable when a less aggregated preparation of Abeta1-42 is used as the immunogen. Importantly, IgG anti-Abeta Ab production is detected after just 12 weeks of Abeta1-42 treatment. Analysis of anti-Abeta 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 Abeta1-42 immunization. To determine the epitope of Abeta recognized by IgG anti-Abeta Abs, intact Abeta and Abeta peptide fragments were analyzed for their ability to bind these Abs. Data show that these Abs specifically recognize an amino-terminal epitope of Abeta between amino acids one and twelve, with higher affinity for a more soluble preparation of Abeta1-42. These data further indicate the immunogenic potential of Abeta1-42 and offer insight into the nature of the IgG anti-Abeta Ab response.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Town T,Tan J,Sansone N,Obregon D,Klein T,Mullan M

doi

10.1016/s0304-3940(01)01951-6

keywords:

subject

Has Abstract

pub_date

2001-07-13 00:00:00

pages

101-4

issue

2

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(01)01951-6

journal_volume

307

pub_type

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