Progressive impairment in olfactory working memory in a mouse model of Mild Cognitive Impairment

Patients with Mild Cognitive Impairment (MCI), exhibiting both working memory and olfactory deficits are likely to progress to Alzheimer's disease (AD). Targeting this pre-clinical AD population with disease modifying agents or cognitive enhancers represents the best strategy for halting or delaying the impact of this pernicious disease. However, there is a paucity of animal models of MCI with which to assess putative therapeutic strategies. We describe an odour span task which assesses the ability of mice to remember lists of odours, and report subtle cognitive deficits in human amyloid over-expressing (Tg2576) mice, at an age prior to plaque deposition. Four-month-old Tg2576 mice exhibited normal acquisition and performance in the standard 12-span task, but were significantly impaired when memory load was increased to 22 odours. By 8-months, a performance deficit was apparent in the 12-span task and by 1-year mice also exhibited significant acquisition deficits. Thus, by assessing olfactory working memory in Tg2576 mice we can model aspects of MCI in rodents and aid development of future therapeutic strategies for AD.