Abstract Body: Introduction: The prevalence of social isolation (SI) increases with aging and contributes to poor health outcomes and increased risk of cognitive impairment, especially in Aβ-related diseases. Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) deposition in the cortical and leptomeningeal vessels, and is a leading cause of hemorrhagic stroke and age-related cognitive impairment. How social isolation affects vascular amyloid deposition, cognitive decline and social behavior in CAA is unknown.

Methods: TgSwDI mice carrying Swedish, Dutch, and Iowa mutations of human amyloid precursor protein were used as a CAA model. Male and female C57BL/6 wildtype (WT) and CAA mice were randomly assigned to pair housing (PH) or SI at 3 months of age. Affective and social behaviors were assessed at baseline and every 3 months thereafter using the tail suspension test (TST) and three-chamber social interaction test. At 9 months post-SI, cognitive behaviors and general well-being were measured using fear conditioning (FC) and the nesting test, respectively. Body weights were recorded, and white adipocyte size was measured using immunostaining.

Results: SI led to increased immobility in the TST at 3- and 6-months post-SI in both male and female WT and CAA mice, suggesting depressive-like behavior (n=5-8/grp, p<0.05). Isolated CAA mice displayed greater cognitive deficits in FC, while only male WT SI mice showed impaired cognition (n=5-12/grp, p<0.005). Sex differences in social behavior were observed in isolated CAA mice. Specifically, at 6 months post-SI, female CAA mice displayed deficits in sociability and social novelty (n=4-9/grp, p<0.05), which was not seen in male CAA mice. SI negatively impacts the general well-being in both male WT and CAA SI animals (n=5-12/grp, p<0.005). Preliminary findings showed increased white adipocyte size in male WT SI mice with a similar trend in male CAA SI animals, pointing to potential metabolic effects of isolation.

Conclusion: SI induced cognitive decline in both male and female CAA mice. Behavioral differences between sexes were noted in CAA mice including nesting ability, sociability, and depressive-like behaviors. Further research is needed to determine the cellular and molecular mechanism underlying SI-induced metabolic changes in CAA.