Fine Social Discrimination of Siblings in Mice: Implications for Early Detection of Alzheimer's Disease

Abstract

The ability to distinguish between individuals is crucial for social species and supports behaviors such as reproduction, hierarchy formation, and cooperation. In rodents, social discrimination relies on memory and the recognition of individual-specific cues, known as "individual signatures". While olfactory signals are central, other sensory cues --such as auditory, visual, and tactile inputs -- also play a role. However, little research has explored the fine discrimination of individuals with overlapping cues, such as siblings or cohabitating mice. This study investigates whether mice can discriminate between two closely related individuals: siblings from the same litter and cage. We tested the hypothesis that it would be more challenging for mice to distinguish between siblings than between unrelated mice due to shared cues. Moreover, social cognitive impairments are common in neurodegenerative diseases like Alzheimers disease (AD), where difficulties in recognizing faces and voices progressively disrupt social interactions in patients. Using a mouse model of AD (Tg2576), known for the progressive onset of cognitive deficits, we assessed whether the ability to discriminate between siblings is preserved in "pre-symptomatic" animals. Thus, we first demonstrated that male and female C57BL6/J mice can discriminate siblings, regardless of sex. Next, we revealed that "pre-symptomatic" 3-month-old Tg2576 mice exhibit impairments in fine social memory, while their general social memory remains unaffected. Thus, we demonstrate that the inability to perform fine social discrimination is an early cognitive impairment that arises before other well-documented memory abnormalities in this AD mouse model. SIGNIFICANCE STATEMENTDiscriminating between individuals is vital for social species, supporting reproduction, hierarchy formation and cooperation. This study examined whether mice can perform fine social discrimination, i.e., distinguish between siblings from the same home cage. We found that both male and female C57BL6/J mice can discriminate siblings, regardless of their sex. Notably, this fine social discrimination ability is impaired in mouse model of Alzheimers disease (AD) at a very early stage of the pathology, i.e., at an age when they can still recognize two unrelated mice from different home cages. This suggests that fine social discrimination deficits occur early in AD, and could serve as an early marker of the pathology.