Variation in Group Composition Alters an Early-Stage Social Phenotype in hAPP-Transgenic J20 Mice

J Alzheimers Dis. 2023;93(1):211-224. doi: 10.3233/JAD-221126.

Abstract

Background: Altered social behavior is one of the symptoms of Alzheimer's disease (AD) that results in social withdrawal and loneliness and provides a major burden on patients and their relatives. Furthermore, loneliness is associated with an increased risk to develop AD and related dementias.

Objective: We aimed to investigate if altered social behavior is an early indicator of amyloid-β (Aβ) pathology in J20 mice, and if co-housing with wild type (WT) mice can positively influence this social phenotype.

Methods: The social phenotype of group-housed mice was assessed using an automated behavioral scoring system for longitudinal recordings. Female mice were housed in a same-genotype (4 J20 or WT mice per colony) or mixed-genotype (2 J20 mice + 2 WT mice) colony. At 10 weeks of age, their behavior was assessed for five consecutive days.

Results: J20 mice showed increased locomotor activity and social sniffing, and reduced social contact compared to WT mice housed in same-genotype colonies. Mixed-genotype housing reduced the social sniffing duration of J20 mice, increased social contact frequency of J20 mice, and increased nest hide by WT mice.

Conclusion: Thus, altered social behavior can be used as an early indicator of Aβ-pathology in female J20 mice. Additionally, when co-housed with WT mice, their social sniffing phenotype is not expressed and their social contact phenotype is reduced. Our findings highlight the presence of a social phenotype in the early stages of AD and indicate a role for social environment variation in the expression of social behavior of WT and J20 mice.

Keywords: Alzheimer’s disease; amyloid; gene-environment interaction; mice; social behavior; social environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor* / genetics
  • Animals
  • Disease Models, Animal
  • Female
  • Mice
  • Mice, Transgenic
  • Phenotype

Substances

  • Amyloid beta-Protein Precursor
  • Amyloid beta-Peptides