title: Adeno-associated Viral (AAV) Serotype 5 Vector Mediated Gene Delivery of Endothelin-converting Enzyme Reduces Aβ Deposits in APP + PS1 Transgenic Mice.
abstract: Reduction of Aβ deposition is a major therapeutic strategy in Alzheimer's disease (AD). The concentration of Aβ in the brain is modulated not only by Aβ production but also by its degradation. One of the proteases involved in the degradation of Aβ peptides is endothelin-converting enzyme (ECE). In this study, we investigated the effects of an intracranial administration of a seroptype 5 recombinant adeno-associated viral vector (rAAV) containing the ECE-1 synthetic gene on amyloid deposition in amyloid precursor protein (APP) plus presenilin-1 (PS1) transgenic mice. The rAAV vector was injected unilaterally into the right anterior cortex and hippocampus of 6-month-old mice, while control mice received an AAV vector expressing green fluorescent protein (GFP). Immunohistochemical testing for the hemagglutinin (HA) tag appended to ECE revealed strong expression in areas surrounding the injection sites but minimal expression in the contralateral regions. Immunohistochemical tests showed that Aβ decreases in the anterior cortex and hippocampus in mice receiving the ECE synthetic gene. Further, decreases in Congo red positive deposits were also observed in both regions. These results indicate that increasing the expression of β-amyloid degrading enzymes through gene therapy is a promising approach to the treatment of AD.
authors.affiliation: Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, Tampa, Florida, USA.
authors.forename: Niki C
authors.initials: NC
authors.lastname: Carty
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Nash
authors.affiliation: Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, Tampa, Florida, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.affiliation: Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, Tampa, Florida, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Mercer
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Gottschall
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Muzyczka
authors.affiliation: Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, Tampa, Florida, USA.
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Gordon
authors.affiliation: Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Biomedical Sciences, University of South Florida College of Medicine, Tampa, Florida, USA. Electronic address: scientist.dave@gmail.com.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan