Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice--a longitudinal study

Abstract

Using a longitudinal study design, two strains of Alzheimer's disease (AD) model mice, one expressing β-amyloid plaques and one expressing Tau protein-associated neurofibrillary tangles were assessed for olfactory and visuospatial learning and memory and their performance compared to that of age-matched controls. No significant difference between AD and control mice was found in the initial set of olfactory tasks performed at 6 months of age whereas both strains of AD mice performed significantly poorer than the controls in visuospatial learning at this age. Subsequent tests performed on the same individual animals at 7, 8, 9, 11, 13, 15, and 18 months of age also failed to find systematic differences in olfactory performance between AD and control mice. In contrast, the AD mice performed consistently poorer than the controls in visuospatial re-learning tests performed at these ages. With most olfactory tasks, both AD and control mice displayed a marked decrease in performance between testing at 15 and 18 months of age. These results show that the two strains of AD model mice do not display an olfactory impairment in a time course consistent with human AD, but are impaired in visuospatial capabilities. The marked age-related changes observed with the olfactory tasks in both AD and control mice suggest that the observed lack of an AD-related olfactory impairment is not due to an insensitivity of the tests employed. Rather, they suggest that the olfactory system of the two AD mouse model strains may be surprisingly robust against AD-typical neuropathologies.

Figure 1. Performance in the seven initial olfactory tasks performed at six months of age.

Each data point [control mice (circles), Tau mice (squares), and Swede mice (triangles)] represents the percentage (mean ± SD) of correct decisions per task across the first five blocks of 20 trials performed per animal and task (left panel), and in the first block of 20 trials (right panel). Task numbers as in Table 2. The dotted line indicates the chance level of performance.

Figure 2. Performance in the visuospatial learning task performed at six months of age.

Each data point [control mice (circles), Tau mice (squares), and Swede mice (triangles)] represents the percentage (mean ± SD) of correct decisions per animal and day. The dotted line indicates the chance level of performance.

Figure 3. Performance in four different olfactory tasks performed at 7, 8, 9, 11, 13, 15, and 18 months of age.

Each data point [control mice (circles), Tau mice (squares), and Swede mice (triangles)] represents the percentage (mean ± SD) of correct decisions across the five blocks of 20 trials performed per animal and task (left panel), and in the first block of 20 trials (right panel). The dotted line indicates the chance level of performance.

Figure 4. Performance in the visuospatial memory task performed at 7, 8, 9, 11, 13, 15, and 18 months of age.

Each data point [control mice (circles), Tau mice (squares), and Swede mice (triangles)] represents the percentage (mean ± SD) of correct decisions across the seven days of testing (left panel), and on the first day of testing (right panel). The dotted line indicates the chance level of performance.

Figure 5. Performance in the olfactory habituation/dishabituation task performed at 18 months of age.

Each data point [control mice (circles), Tau mice (squares), and Swede mice (triangles)] represents the investigation time (mean ± SD) in seconds during four consecutive 2-minute presentations of an odorant A followed by one 2-minute presentation of a novel odorant B.

Figure 6. Histology.

After fixation of 18 month-old animals, 50 µm coronal sections were stained with Thioflavin T to label β-amyloid plaques. A) Swede mouse. White arrows indicate plaques in the orbital frontal cortex and anterior olfactory cortex, respectively. B) 18 month-old control mouse without any plaque staining. C) A Z-stack showing a 10 µm diameter plaque, one of the larger ones observed. D) A middle tufted cell of the olfactory bulb showing Tau tangle phenotype in a tested Tau mouse.