Abstract TP161: Social Isolation Increases Liver Inflammation and Alters Hepatocyte Morphology in Cerebral Amyloid Angiopathy

Abstract

Introduction: Social isolation (SI) is a growing yet understudied public health concern. Accumulating evidence suggests that SI has critical psychological implications and can also lead to considerable negative physiological outcomes, as in the case of cerebral amyloid angiopathy (CAA). CAA is characterized by the accumulation of amyloid-beta (Aβ) in the leptomeningeal vessels, which compromises the integrity of cerebral vasculature, thus increasing risk of intracerebral hemorrhages. Our preliminary data suggests SI induces metabolic changes including average weight gain in CAA mice compared to pair-housed (PH) counterparts (30g vs 25g, respectively; p<0.01). Hence, it is imperative to investigate the effects of social isolation on liver physiology and energy metabolism in the context of CAA. Hypothesis: We hypothesize that SI leads to decreased Aβ clearance by the liver, and increased immune cell infiltration into the liver. Methods: 3-month-old C57BL/6 (WT, n=21) and TgSwDI mice (n=21) were either pair-housed (PH) or socially-isolated (SI) for 9 months. We assessed Aβ deposition, hepatocyte morphology, vascular structure, and liver immune cell composition through immunohistochemistry. We additionally quantified ALT/AST levels and LRP-1 levels as a measure of liver dysfunction and Aβ clearance, respectively. Neurobehavioral performance was measured by nesting and tail-suspension test. Results: Our findings show that socially isolated CAA mice exhibit sustained affective and cognitive impairments when compared to the PH group. Average nesting scores are significantly lower for male CAA SI mice compared to PH mice (1.67 vs 3.5, respectively; p<0.01). SI CAA mice have larger hepatocytes and increased immune cell infiltration when compared to the PH counterparts and WT controls. Furthermore, Aβ signals were found to colocalize with liver-resident macrophages, implying a role of amyloid clearance by these cells. Discussion: Together we show that SI increases body weight and inflammation, and exacerbates cognitive and behavioral deficits. These changes may affect AB clearance, thereby potentially worsening CAA pathology. Further investigation into liver energy metabolism and macrophage-mediated inflammation is warranted.