Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease

Stephen R Edwards, Adam S Hamlin, Nicola Marks, Elizabeth J Coulson, Maree T Smith

Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's Disease (AD) requires an animal model that develops age{\hyphen}related cognitive deficits reproducibly between independent groups of investigators. Herein, we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD, using the Morris water maze (MWM) incorporating both visible and hidden platform training. Individual cohorts of cDNA{\hyphen}based 'line 85'{\hyphen}derived double transgenic mice co{\hyphen}expressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages 3.6, 9.3, and 14.8 months. We found significant deficits in spatial memory retention in APPSwe{\sol}PS1dE9 mice aged 3.6 months, and robust deficits in spatial memory acquisition and retention in APPSwe{\sol}PS1dE9 mice aged 9.3 months, with a further significant decline by age 14.8 months. β{\hyphen}amyloid deposits were present in brain sections by age 7.25 months. By contrast, MWM studies with individual cohorts (aged 4{\hyphen}21 months) of single transgenic genomic{\hyphen}based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct, showed no significant deficits in spatial memory acquisition until age 21 months. There were no significant deficits in spatial memory retention up to age 21 months, and β{\hyphen}amyloid deposits were not present in brain sections up to age 24 months. Our data generated using comprehensive study designs show that APPSwe{\sol}PS1dE9 but not APPSwe YAC mice, appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development. This article is protected by copyright. All rights reserved.