title: Peripheral transgene expression of plasma gelsolin reduces amyloid in transgenic mouse models of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Hirko
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Hughes
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000628:therapy*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018260:Gelsolin / Q000097:blood / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000682:Amyloid; D018260:Gelsolin