Reduction in open field activity in the absence of memory deficits in the AppNL−G−F knock-in mouse model of Alzheimer’s disease

Abstract

The recent development of knock-in mouse models of Alzheimer’s disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer’s researchers are the AppNL−F and AppNL−G−F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of AppNL−G−F/NL−G−F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between AppNL−G−F/NL−G−F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between AppNL−G−F/NL−G−F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of AppNL−G−F/NL−G−F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in AppNL−G−F/NL−G−F knock-in brain.