Apathy-like behaviour in tau mouse models of Alzheimer's disease and frontotemporal dementia

Abstract

Apathy is the most common behavioural and psychological symptom in Alzheimer's disease (AD) and other neurodegenerative diseases including frontotemporal dementia (FTD) and Parkinson's disease (PD). In patients, apathy can include symptoms of loss of motivation, initiative, and interest, listlessness, and indifference, flattening of emotions, absence of drive and passion. Researchers have later refined this to a reduction in goal direct behaviours. In animals, specific symptoms of apathy-like behaviour have been modelled including goal directed or nest-building behaviour which are seen as indicative of proxies for motivation and daily activities. In the present study a nest-building protocol was established using four different inbred mouse strains (CD1, BALB/c, C57Bl/6J, C3H) before assessing AD and FTD tau transgenic mice of Line 1 (L1) and Line 66 (L66) in this paradigm. Female mice aged 5 - 6 months were assessed in the home cage over a period of 7 days with nest-building behaviour scored by three independent experimenters at intervals of 1-, 2- and 7-days post nestlet introduction. Inbred mouse strains displayed different levels of nesting behaviour. BALB/c mice were more proficient than CD1 and C3H mice, while all strains displayed similar nest-building behaviour by day 7. In the tau mouse models, L66 presented with impaired nesting compared to wild-type on days 1 and 2 (not day 7), whereas L1 performed like wild-type on all days. Anhedonia measured in a sucrose preference test was only observed in L66. Anhedonia and low nesting scores in L66 mice are indicative of apathy-like phenotypes. Differences evident between the L1 and L66 tau transgenic mouse models are likely due to the different human tau species expressed in these mice.

Keywords: Apathy; Dementia; Mouse; Nest building; Tau.