Assessment of apathy‐like behaviour in transgenic mouse models of neurodegenerative diseases

Abstract

AbstractBackgroundApathy is the most common behavioural and psychological symptom in neurodegenerative diseases like Alzheimer’s disease (AD), frontotemporal dementia (FTD) or Parkinson’s disease (PD). Apathy typically includes a loss of motivation, initiative and interest, listlessness and indifference, flattening of emotions, absence of drive and passion. Scientists have defined this as a reduction/lack in goal direct behaviour. There are currently no specific treatment options for apathy. In experimental models, selective symptoms of apathy‐like behaviour are measured in goal directed or nesting behavioural tasks, which report on their motivation to perform daily activities. A richer understanding of apathy, however, may be achieved through the development of a battery of tests including goal directed, nesting, anhedonia, activity monitoring, and social interaction. These have been applied here to several animal models of neurodegeneration.MethodMale and female transgenic mice (aged 6 – 8 months) including tau over‐expressors L1 for AD and L66 for FTD (Melis et al. 2015); PLB4 BACE1 mouse model for AD (Plucinska et al. 2014); L62 alpha‐synuclein mouse model of PD (Frahm et al. 2018) and relevant wild type (WT) controls were utilised in this study. Animals were tested in a series of behavioural tests including the nest building task, sucrose preference test, buried cookie test, social interaction, and home cage activity. Performance was recorded and analysed by behavioural tracking software as indicators of apathy‐like behaviour.ResultTwo models showed reproducible results compared with previous studies. Intriguingly, L66 FTD mice presented with deficits in sucrose preference and nest‐building, but not a lowering of general activity. Although this was not found for the sister strain, L1 mice which has AD‐like pathology. Very much unexpected is the observation that neither the amyloid nor the synuclein‐based models showed any significant behavioural anomalies. Further detailed investigations are ongoing.ConclusionInitial observations have confirmed that the transgenic models for neurodegenerative diseases show different levels of apathy‐like behaviour. It appears that the phenotype in L66 is a tau‐related anomaly specific to the tau species expressed, i.e. the mutation at P301S. The lack of deficits in all other models warrants in‐depth confirmation and analysis.