There were also no anxiety-related behavior deficits check FAQ seen at any age in the APP/PS1 KI mice in the elevated plus maze tasks. This is in contrast to the Tg2576, J20, APP/PS1, and 5xFAD mice, which all were found to have increased anxiety-related behavior in the elevated plus maze task. In the open field task, animals with elevated anxiety levels will spend little time exploring the center of the chamber [30,32]. The APP/PS1 KI mice do not exhibit anxiety-related behavior, as they showed normal exploration of the center of the open field chamber. Anxiety behavior did not differ between APP/PS1 KI mice and WT mice for any age tested. Our results therefore demonstrate that there are no deficits in either motor function or anxiety levels that could potentially confound cognitive testing in this mouse model of AD, which is dissimilar to the majority of the mouse models shown in Figure ?Figure44.

Attempts to model AD-relevant cognitive deficits in mouse models have met with some degree of success [33,34]. Reference memory is a type of memory that is often assessed in various mouse models of AD because deficits in this type of memory are highly specific for hippocampal function (one of the earliest/most severely affected brain regions in human AD) [35]. One common method for assessing deficits in hippocampal-based reference memory is through the use of exploration-based memory tasks such as the Morris water maze and the RAWM [33]. Here we observe deficits in spatial reference memory for the APP/PS1 KI mice when tested in the RAWM.

These deficits in spatial reference memory are first evident in the 11 month age group, and continue to progress as the age/pathology increases in this model. The temporal onset and progression of cognitive impairment compared with other commonly used AD mouse models can be seen in Figure ?Figure4.4. For example, compared with other APP and PS1 AD mouse models, such as the APP/PS1 model and the APP + PS1 model, the onset of cognitive deficits in the APP/PS1 KI model appears to occur slightly later in life. Both the APP + PS1 model and the APP/PS1 model show deficits at 4 to 6 months of age [36-39], whereas the APP/PS1 KI mice show deficits starting at 11 months old (Figure ?(Figure33). Another commonly tested type of AD-relevant memory is that of recognition memory. The most common way to assess recognition memory in mice is through the use of the NOR task [33].

Here we see cognitive impairment Cilengitide in the NOR task manifest in the APP/PS1 KI model at 15 months of worldwide distributors age. As shown in Figure ?Figure4,4, this temporal pattern is similar to the onset of NOR deficits in some other AD mouse models, such as the Tg2576 mice and the APP + PS1 model. In contrast, some mouse models such as the PDAPP, APP23, TgCRND8, J20, 5xFAD, and 3xTG-AD mice show impairment in recognition memory at a younger age.