Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's disease

Bilirubin, an efficient antioxidant, is the end product of the heme cleavage pathway, which is catalyzed by heme oxygenase (HO) and biliverdin reductase. Although an inducible form of HO is overexpressed in the Alzheimer's disease (AD) brain, it has not been determined whether bilirubin metabolism is actually activated or not. In this study, we measured CSF-bilirubins and their derivatives using an enzyme-linked immunosorbent assay with two kinds of anti-bilirubin monoclonal antibodies, designated 24G7 and 5M2. In AD patients, the levels of CSF bilirubin derivatives increased significantly compared with those of controls. This increase was not due to the increased permeability of the blood-brain barrier, because the levels of unconjugated bilirubin were not different between AD and controls. These data may reflect the increase of degraded bilirubin metabolites in the AD brain derived from the scavenging reaction against chronic oxidative stress.