Activation of early components of complement targets myelin and oligodendrocytes in the aged rhesus monkey brain

The disruption and loss of myelin in the white matter are some of the major changes that occur in the brain with age. In vitro studies suggest a role of the complement system in the catabolic breakdown of myelin membranes. This study presents findings on activation of the early components of complement cascade in the brains of both young and aged rhesus monkeys with evidence of increased complement activation in aged animals. Complement containing oligodendrocytes (CAOs) containing C3d and C4d complement activation products bound to oligodendrocytes and myelinated fibers were found in the brain of normal young and old animals. The CAOs, which also contained activated microglia, were distributed throughout the whole brain and in significantly greater numbers in the aged monkeys. These findings, together with the demonstration of covalent binding of the C3 fragments to myelin, suggest the initiation of the complement cascade by myelin and oligodendrocytes, which are known classical complement activators. Activation of terminal complement components was not demonstrable in the CAOs. Taken together the findings support the concept that activation of early components of complement in the brain may be a normal biological process that involves the metabolism of myelin and oligodendrocytes and up-regulates with age.