Characterization of apathy-like behaviors in the 5xFAD mouse model of Alzheimer’s disease

Most patients with Alzheimer’s disease (AD) develop neuropsychiatric symptoms (NPS) alongside cognitive decline, and apathy is one of the most common symptoms. Few preclinical studies have investigated the biological substrates underlying NPS in AD. In this study, we used a cross-sectional design to characterize apathy-like behaviors and assess memory in 5xFAD and wildtype control mice at 6, 12, and 16 months of age. Nest building, burrowing, and marble burying were used to test representative behaviors of apathy, and a composite score of apathy-like behavior was generated from these assays. Soluble Aβ42 and plaques were quantified in the prefrontal cortex and hippocampus of the 5xFAD mice with the highest and lowest composite scores using ELISA and histology. Results suggest that 5xFAD mice develop significant apathy-like behaviors starting at 6 months of age that worsen with aging and are positively correlated with soluble Aβ42 and plaques in the prefrontal cortex and hippocampus. Our findings highlight the utility of studying NPS in mouse models of AD to uncover important relationships with underlying neuropathology.