A monoclonal antibody against synthetic Aβ dimer assemblies neutralizes brain-derived synaptic plasticity-disrupting Aβ.

ABSTRACT: Diverse lines of evidence indicate that pre-fibrillar, diffusible assemblies of the amyloid β-protein (Aβ) play an important role in Alzheimer's disease pathogenesis. Although the precise molecular identity of these soluble toxins remains unsettled, recent experiments suggest that sodium dodecyl sulfate (SDS)-stable Aβ dimers may be the basic building blocks of Alzheimer's disease-associated synaptotoxic assemblies and as such present an attractive target for therapeutic intervention. In the absence of sufficient amounts of highly pure cerebral Aβ dimers, we have used synthetic disulfide cross-linked dimers (free of Aβ monomer or fibrils) to generate conformation-specific monoclonal antibodies. These dimers aggregate to form kinetically trapped protofibrils, but do not readily form fibrils

SUBMITTER: O'Nuallain B 

PROVIDER: S-EPMC3174526 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature