Complement Activation in Capillary Cerebral Amyloid Angiopathy

Abstract

Background: Cerebral amyloid angiopathy (CAA) is classified as type 1 with capillary amyloid β (Aβ) or type 2 without capillary Aβ. While it is known that CAA activates complement, an inflammatory mediator, there is no information on the relationship between capillary Aβ and complement activation. Methods: We evaluated 34 autopsy brains, including 22 with CAA and 12 with other neurodegenerative diseases. We assessed the vascular density of CAA by analyzing the expression of complement (C1q, C3d, C6, C5b-9), macrophage scavenger receptor (MSR), and apolipoprotein E (ApoE). Results: Capillary immunostaining for C1q, C3d, MSR, and ApoE was identified almost exclusively in CAA-type1 brains. There was intense expression of C1q, C3d, MSR, and ApoE, as well as weaker expression of C5b-9 and C6 in the arteries/ arterioles of both CAA subtypes, but not in control brains. C5b-9 and C6 were preferentially expressed in arteries/arterioles with subcortical hemorrhage or cortical superficial siderosis. Triple immunofluorescence revealed that C1q, C3d, and ApoE were colocalized with Aβ in CAA brain capillaries. Conclusion: Complement, MSR, and ApoE were only coexpressed in the presence of Aβ accumulation in capillaries, suggesting a role for complement activation in the propagation of Aβ. Additionally, C5b-9 expression may be associated with hemorrhagic brain injury in CAA.