Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Aβ deposits in APP + PS1 transgenic mice

Niki C. Carty, Kevin Nash, Daniel Lee, Mary Mercer, Paul E. Gottschall, Craig Meyers, Nicholas Muzyczka, Marcia N. Gordon, Dave Morgan

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish
Pages (from-to)1580-1586
Number of pages7
JournalMolecular Therapy
Volume16
Issue number9
DOIs
StatePublished - 2008

Bibliographical note

Funding Information:
Supported by The Johnnie Byrd Center for Alzheimer’s Research, NIH grants AG-25509, AG 15490, AG 18478, AG 04418, AG 25711.

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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