Document Detail

Peripheral transgene expression of plasma gelsolin reduces amyloid in transgenic mouse models of Alzheimer's disease.
MedLine Citation:
PMID:  17609655     Owner:  NLM     Status:  MEDLINE    
The accumulation and deposition of the 40-42-amino acid peptide amyloid beta (Abeta) is thought to be a critical event in the pathology of Alzheimer's disease (AD). Both passive and active immunizations against Abeta in amyloid-depositing transgenic mice have reduced Abeta pathology and improved memory-related behavior. Peripheral treatments with other amyloid-binding agents have also reduced Abeta pathology. The present study demonstrates that peripheral delivery of plasmid DNA coding for the amyloid-binding protein plasma gelsolin reduces brain Abeta in two separate amyloid-depositing transgenic mouse models of AD when inter-litter variability is accounted for. The reduction in Abeta pathology observed is accompanied by an apparent increase in activated and reactive microglia and soluble oligomeric forms of amyloid. These findings demonstrate that peripheral expression of plasma gelsolin may be a suitable gene-therapeutic approach for the prevention or treatment of AD.
Aaron C Hirko; Edwin M Meyer; Michael A King; Jeffery A Hughes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-07-03
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  15     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-21     Completed Date:  2008-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1623-9     Citation Subset:  IM    
Department of Pharmaceutics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA.
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MeSH Terms
Alzheimer Disease / pathology,  therapy*
Amyloid / metabolism*
Blotting, Western
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Gelsolin / blood,  genetics*,  physiology
Gene Therapy / methods*
Mice, Transgenic
Microglia / metabolism,  pathology
Plasmids / genetics
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Amyloid; 0/Gelsolin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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