A functional role for corpora amylacea based on evidence from complement studies

Abstract

Few theories have been advanced for the production of corpora amylacea (CA) by the normal ageing brain and by the CNS under various neurological conditions. Proteins derived from neurons and oligodendrocytes are found in CA and to understand their origins brain tissue from patients with Alzheimer's disease (AD), multiple sclerosis (MS) and Pick's disease (PD) were tested for complement activity. All CA were immunopositive for antisera to classical pathway-specific components, the activation products C3d and the terminal complement complex (TCC), the C3 convertase regulator membrane cofactor protein (MCP) and the fluid phase regulators S-protein and clusterin. CA were immunonegative for the alternative complement pathway proteins and the complement regulators, decay accelerating factor (DAF) and CD59. Western immunoblotting of isolated solubilized CA from the same tissues demonstrated a week band for MCP but TCC was more easily shown by immunoprecipitaton. A filamentous fringe around CA, probably of astrocytic origin, was also immunopositive for complement factors. CA consist of an inert mucopolysaccharide matrix encasing ubiquitinated proteins, resulting from death of and damage to neurons, myelin and oligodendrocytes. A function of CA, therefore, could be to prevent the recognition of these immunogenic proteins by lymphocytes and microglia and thus protect the CNS from further injury.