Affective and cognitive deficits in a novel AD mouse model: A role for noradrenaline and inflammation

Abstract

AbstractBackgroundDepression has been robustly linked to Alzheimer’s disease (AD) often occurring before the onset of cognitive decline. The affective symptoms that accompany this decline are also frequently overlooked but could offer insights into the early stages of the disease and how it progresses. To examine this link in detail, animal models are good at offering a controlled and detailed assessment which could uncover whether affective insults are merely a symptom or play a significant role in disease onset. Furthermore, gender is rarely considered despite being an important risk factor for AD so understanding sex differences in disease progression will further aid this mechanistic research. For these reasons, assessing the affective and cognitive deficits of an AD mouse model will be compared to neurological insults of relevant brain areas (i.e. Locus Coeruleus (LC)) and inflammation.MethodUsing a novel Knock‐in mouse model, the AppNL‐G‐F , behavioural analysis was used to examine affective deficits in a young cohort (n=96) aged 5‐7 months using Open field, Object in Place, Social preference test, elevated plus maze and Lick Cluster analysis. Immunohistochemistry stain for Tyrosine Hydroxylase will show any insults to the LC while a plaque and microglia stain will spatially show the inflammatory response around amyloid aggregation.ResultAt this early time point, no affective deficits were found aside from a reduction in distance moved by the AppNL‐G‐F in the open field which could be indicative of a depressive‐like symptom but, in the absence of other deficits, will be taken at face value. There were no significant gender differences in any of the tests and this absence of behavioural effects are examined in relation to degree of neurological insult.ConclusionAs expected, the young cohort’s lack of behavioural deficits mean they offer a good baseline before AD insult to contrast with an older (12‐14 months) cohort. This comparison is in progress assess affective symptom progression in relation to LC damage, inflammation and amyloid pathology.