title: Cognitive evaluation of disease-modifying efficacy of donepezil in the APP23 mouse model for Alzheimer's disease.
abstract: BACKGROUND
  The interest for acetylcholinesterase inhibitors in the treatment of Alzheimer's disease has been greatly renewed owing to the discovery of a broad range of additional cholinergic and non-cholinergic effects, exploitable to maximize the efficacy of these drugs beyond merely improving intellectual functions at the symptomatic level.
  
  
  OBJECTIVE
  The age-dependent cognitive decline in the valid APP23 transgenic mouse model for Alzheimer's disease was employed to evaluate disease-modifying efficacy of chronic treatment with donepezil.
  
  
  METHODS
  At age 6 weeks, heterozygous APP23 mice and control littermates were subcutaneously implanted with osmotic pumps delivering saline or donepezil (0.27 or 0.58 mg/kg per day). After 2 months of treatment, a 3-week wash-out period was allowed to prevent bias from sustained symptomatic effects before cognitive evaluation in the Morris water maze commenced.
  
  
  RESULTS
  Donepezil (0.27 mg/kg per day)-treated APP23 mice performed significantly better than their sham-treated counterparts during the Morris water maze acquisition phase and the subsequent probe or retention trial. Chronic donepezil (0.27 mg/kg per day) treatment improved spatial accuracy in APP23 mice as to reach the same level of performance as wild-type control animals on this complex visual-spatial learning task.
  
  
  CONCLUSIONS
  This is the first study reporting disease-modifying efficacy of donepezil at the level of cognitive performance in transgenic mice modeling Alzheimer's disease.
authors.affiliation: Department of Biomedical Sciences, Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.forename: Katrien
authors.initials: K
authors.lastname: Coen
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D005838:Genotype; D007189:Indans / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D009949:Orientation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil