Immune Activation in Amyloid-β-Related Angiitis Correlates with Decreased Parenchymal Amyloid-β Plaque Load

Background: Primary angiitis of the central nervous system (PACNS) is a rare but serious condition. A fraction of patients suffering from PACNS concurrently exhibit pronounced cerebral amyloid angiopathy (CAA) which is characterized by deposits of amyloid-beta (A beta) in and around the walls of small and medium-sized arteries of the brain. PACNS with CAA has been identified as a distinct disease entity, termed A beta-related angiitis (ABRA). Evidence points to an immune reaction to vessel wall A beta as the trigger of vasculitis. Objective: To investigate whether the inflammatory response to A beta has (1) any effect on the status of immune activation in the brain parenchyma and (2) leads to clearance of A beta from brain parenchyma. Methods: We studied immune activation and A beta load by quantitative immunohistochemical analysis in brain parenchyma adjacent to affected vessels in 11 ABRA patients and 10 matched CAA controls. Results: ABRA patients showed significantly increased immune activation and decreased A beta loads in the brain parenchyma adjacent to affected vessels. Conclusion: Our results are in line with the hypothesis of ABRA being the result of an excessive immune response to A beta and show that this can lead to enhanced clearance of A beta from the brain parenchyma by immune-mediated mechanisms. (C) 2013 S. Karger AG, Basel