Figure 2 Anxiety-related behavior Volasertib mw of APP/PS1 KI and wild-type control mice. (A) No difference in the time spent exploring in the center zone between the amyloid precursor protein/presenilin-1 knock-in (APP/PS1 KI) mice and the wild-type (WT) mice was observed … Cognitive behavior The cognitive behavior of APP/PS1 KI and WT mice was tested in the RAWM and NOR behavioral tasks – tests that measure spatial reference memory and recognition memory, respectively. In the RAWM, there was no difference in performance between APP/PS1 KI mice and WT mice at 7 months of age (Figure ?(Figure3A).3A). In contrast, APP/PS1 KI mice aged 11 months old (Figure ?(Figure3B),3B), 15 months old (Figure ?(Figure3C),3C), and 24 months old (Figure ?(Figure3D)3D) performed significantly worse in the RAWM task than did the WT mice of the same ages.

When the RAWM maze data are analyzed as a function of errors made versus age of the animals (Figure ?(Figure3E),3E), it is evident that APP/PS1 KI mice progressively increase the number of errors they make as they age (and the disease progresses). Figure 3 Cognitive behavior of APP/PS1 KI and wild-type control mice. Radial arm water maze (RAWM) performance for each age group: (A) no observable difference is seen between amyloid precursor protein/presenilin-1 knock-in (APP/PS1 KI) mice and wild-type (WT) … In the NOR behavior task, the APP/PS1 KI and WT mice both showed a clear preference for novel object exploration during the dissimilar stimuli (A/B) session compared with the familiar at the ages of 7 and 11 months old (Figure ?(Figure3F).3F).

However, in the groups of 15 and 24 month olds, the APP/PS1 KI mice lost the ability to discriminate between familiar and novel objects and were significantly impaired compared with the WT controls (P = 0.044 for 15 month olds, P = 0.041 for 24 month olds). Each animal tested had an exploration time >10 seconds with each object, Cilengitide and no significant difference in movement speed (velocity range: 2.4 to 3.6 cm/second) was observed between genotypes or age groups. When the NOR task data are analyzed as a function of the D2 recognition index versus age of the animals (Figure ?(Figure3G),3G), it is evident that APP/PS1 KI mice also become progressively impaired in this task as they age and the AD-relevant pathology progresses.

Discussion Many lines of genetically altered mice have been generated during the past few decades in an effort to better understand the pathogenesis of AD. These mouse models of AD http://www.selleckchem.com/products/AG-014699.html pathobiology have provided significant neuropathological, biochemical, physiological, and behavioral insights into AD pathogenesis. Many of the AD mouse models differ in the site of the mutation in APP, or in the number of APP mutations in one mouse, or the addition of mutations in PS1 or tau.