Abstract 62: Increased Monocyte/Macrophage Pro-Inflammatory Cytokines and Chemokines in Mice With Cerebral Amyloid Angiopathy
Introduction: Cerebral amyloid angiopathy (CAA) is one of the common causes of intracerebral hemorrhage in the elderly. It is caused by the deposition of amyloid-beta1-40 (Aβ1-40) deposition within cerebral blood vessels, especially the smooth muscle layer, that can cause cerebral microbleeds (CMBs) and cognitive impairment. We hypothesize Aβ deposition causes an innate inflammatory response characterized by an increase and activation of microglia and macrophages. This inflammation might cause CMBs, neuronal damage and cognitive decline CAA. Methods: C57BL6 Tg-SwDI male and female mice (18 months) were used as a mouse model for CAA. Age-matched wild-type (WT) mice were used as controls. Brain samples from these mice were fractionated and 23-plex cytokine multiplex was performed on the brain lysates. Data was analyzed using two sample t-test or GraphPad PRISM. Results: Our data showed that CAA increased levels of pro-inflammatory cytokines in the brain, as compared with WT mice. Multiplex analysis showed that Tg-SwDI mice had significantly higher levels of cytokines; tumor necrosis factor-α (TNF-α; 54.38 vs. 17.03 pg/ml, p=0.00207), IL-12 (70.81 vs. 53.95 pg/ml, p= 0.014), macrophage inflammatory protein-1α (MIP-1α, 113.92 vs. 16.81 pg/ml, p=3.85E-10), MIP-1β (86.15 vs. 53.43 pg/ml, p= 3.51E-09) and monocyte chemoattractant protein-1 (MCP-1, 109.46 vs. 118.53 pg/ml, p= 0.00033). Conclusion: This study highlights a monocyte/macrophage driven pro-inflammatory milieu in CAA. Recent studies using in vivo two-photon imaging and histology have found recruitment of microglia and monocytes/macrophages around induced 100 μm sized hemorrhage. The increase in these microglia is only found in Alzheimer’s patients who also had CAA and was not seen in patients with no CAA, suggesting the role of microglia in causing vascular frailty in CAA. Our study suggests that pro-inflammatory cytokines like TNF-a, IL-12, MIP-1α, MIP-1β and MCP-1 can be therapeutic targets for CAA.