Epitopes described in "Abeta-directed single-chain antibody delivery via a serotype-1 AAV vector improves learning behavior and pathology in Alzheimer's disease mice."

Article Authors:Deborah A Ryan; Michael A Mastrangelo; Wade C Narrow; Mark A Sullivan; Howard J Federoff; William J Bowers
Article Title:Abeta-directed single-chain antibody delivery via a serotype-1 AAV vector improves learning behavior and pathology in Alzheimer's disease mice.
Reference Detail
Reference ID:1020948
Abstract:Alzheimer's disease (AD) is a progressive dementing disorder characterized by age-related amyloid-beta (Abeta) deposition, neurofibrillary tangles, and synapse and neuronal loss. It is widely recognized that Abeta is a principal pathogenic mediator of AD. Our goal was to develop an immunotherapeutic approach, which would specifically lead to the clearance and/or neutralization of Abeta in the triple transgenic mouse model (3xTg-AD). These mice develop the amyloid and tangle pathologies and synaptic dysfunction reminiscent of human AD. Using a human single-chain variable fragment (scFv) antibody phage display library, a novel scFv antibody specific to Abeta was isolated, its activity characterized in vitro, and its open reading frame subsequently cloned into a recombinant adeno-associated virus (rAAV) vector. Three-month-old 3xTg-AD mice were intrahippocampally infused with serotype-1 rAAV vectors encoding Abeta-scFv or a control vector using convection-enhanced delivery (CED). Mice receiving rAAV1-Abeta-scFv harbored lower levels of insoluble Abeta and hyperphosphorylated tau, and exhibited improved cognitive function as measured by the Morris Water Maze (MWM) spatial memory task. These results underscore the potential of gene-based passive vaccination for AD, and provide further rationale for the development of Abeta-targeting strategies for this debilitating disease.
Affiliations:Interdepartmental Graduate Program in Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
Reference Type:Literature
PubMed ID:20551911
Journal:Mol Ther
Journal Volume:18
Article Pages:1471-81
Journal ISSN:1525-0024
Article Chemical List:Amyloid beta-Peptides;Single-Chain Antibodies
Article MeSH List:Alzheimer Disease(metabolism; pathology; therapy); Amyloid beta-Peptides(immunology); Animals; Cell Survival(genetics; physiology); Cells, Cultured; Cricetinae; Dependovirus(genetics); Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Male; Maze Learning(physiology); Mice; Mice, Transgenic; Single-Chain Antibodies(genetics; metabolism)
Curation Last Updated:2015-06-05 02:29:44