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Cognitive evaluation of disease-modifying efficacy of donepezil in the APP23 mouse model for Alzheimer’s disease

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Abstract

Rationale

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.

Objectives

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.

Materials and 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.

Conclusion

This is the first study reporting disease-modifying efficacy of donepezil at the level of cognitive performance in transgenic mice modeling Alzheimer’s disease.

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Acknowledgment

This work was supported by the Fund for Scientific Research-Flanders (FGWO grant G.0038.05), Interuniversity Poles of Attraction (IUAP Network P6/43), agreement between Institute Born-Bunge and University of Antwerp, the Antwerp Medical Research Foundation, the Thomas Riellaerts Research Fund, Neurosearch Antwerp, and Pfizer. D.V.D. is a postdoctoral fellow of the Fund for Scientific Research–Flanders. K.C. is a PhD fellow of the Fund for Scientific Research-Flanders.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Debby Van Dam, Katrien Coen & Peter Paul De Deyn

  2. Department of Neurology/Memory clinic, Middelheim General Hospital, ZNA, Lindendreef 1, 2020, Antwerp, Belgium

    Peter Paul De Deyn

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  1. Debby Van Dam
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  2. Katrien Coen
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Correspondence to Peter Paul De Deyn.

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Van Dam Debby and Coen Katrien equally contributed to this publication.

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Van Dam, D., Coen, K. & De Deyn, P.P. Cognitive evaluation of disease-modifying efficacy of donepezil in the APP23 mouse model for Alzheimer’s disease. Psychopharmacology 197, 37–43 (2008). https://doi.org/10.1007/s00213-007-1010-x

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  • DOI: https://doi.org/10.1007/s00213-007-1010-x

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