Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer's disease.

INTRODUCTION

Alzheimer's disease (AD) is characterized by progressive cognitive decline and has a long prodromal phase during which subclinical cognitive deficits and neuropsychiatric symptoms may begin to emerge. Apathy, defined as a lack of motivation or volition, is increasingly recognized as a core feature and a potentially early marker of AD. Despite its significance, apathy-like behavior has been underexplored in transgenic models of AD.

METHODS

We performed a longitudinal analysis of apathy-like behavior using the well-established TgF344-AD rat model. We compared male and female TgF344-AD and wildtype rats on hedonic (palatable food intake) and motivational (progressive ratio) assays during early (3-4 months), intermediate (6-7 months), and later (9-10 months) stages of adulthood.

RESULTS

We found that female TgF344-AD rats exhibited early and persistent deficits in motivational and hedonic feeding, emerging at 3-4 months and 6-7 months, respectively. During a battery of cognitive tests conducted after 12-14 months of age, TgF344-AD rats were impaired in spatial working memory but also showed wide-ranging deficits in exploratory behavior, which may also be indicative of an apathy-like loss of investigatory drive.

CONCLUSION

Our findings highlight the TgF344-AD rat as a valuable model for studying early apathy-like behavior in AD and underscore the need to consider sex differences in AD research to better understand the prodromal phase of this disease.