title: A novel rat model of Alzheimer's disease based on lentiviral-mediated expression of mutant APP.
abstract: BACKGROUND
  Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease.
  
  
  METHODS
  Lentiviruses (LV) encoding human amyloid protein precursor (APP) bearing the fAD-linked Swedish and Indiana mutations (APPSw/Ind) were injected bilaterally in the hippocampus of adult rats. Passive avoidance and spatial memory performance were assessed 30 and 45 days post-injection, respectively. APP overexpression, intracellular accumulation of β-amyloid (Aβ) peptide, and astrogliosis were also evaluated using immunohistochemical procedures.
  
  
  RESULTS
  Passive avoidance memory deficit was followed by impairments in spatial memory retrieval in LV (APPSw/Ind)-injected rats, compared to control animals. In addition, LV expression of APPSw/Ind was associated with intraneuronal accumulation of Aβ, and reactive astrocytosis, two major AD hallmarks.
  
  
  CONCLUSIONS
  Results from this work suggest that LV-mediated delivery of APPSw/Ind in adult rats represents a cost and time-effective animal model for the study of mechanisms underlying APP-linked fAD pathogenesis. The relevance of this animal model to the study of sporadic AD is discussed.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Parsi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Pandamooz
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Heidari
authors.affiliation: Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Naji
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Morfini
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: A
authors.initials: A
authors.lastname: Ahmadiani
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: l.dargahi@sbmu.ac.ir.
authors.forename: L
authors.initials: L
authors.lastname: Dargahi
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar
chemical_list: D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein
keywords: Alzheimer’s disease; animal model; lentiviral vector