Journal
NEUROBIOLOGY OF DISEASE
Volume 23, Issue 3, Pages 502-511Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.04.012
Keywords
gene therapy; vaccine; amyloid protein; amyloid plaque; transgenic mouse; immune therapy
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Funding
- NINDS NIH HHS [R01 NS043947, R01 NS043947-04, NS43947] Funding Source: Medline
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Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (A) reduces A beta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of anti-A beta F(ab')2 antibodies also induces clearance of amyloid plaques in AD mouse models, we have tested a novel gene therapy modality where an adeno-associated virus (AAV) encoding anti-alpha single-chain antibody (scFv) is injected into the corticohippocampal regions of AD mouse models. One year after injection, expression of scFv was readily detectable in the neurons of the hippocampus without discernible neurotoxicity. AD mouse models subjected to AAV injection had much less amyloid deposits at the injection sites than the mouse models subjected to PBS injection. Because the scFv lacks the Fc portion of the immunoglobulin molecule, this modality may be a feasible solution for AD without eliciting inflammation. (c) 2006 Elsevier Inc. All rights reserved.
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