Ultrastructural localization of complement membrane attack complex (MAC)-like immunoreactivity in brains of patients with Alzheimer's disease

Abstract

The membrane attack complex (MAC) of complement, also known as C5b-9, was localized in Alzheimer's disease (AD) brain by immunoelectron microscopy using a monoclonal antibody to a neoantigenic epitope of soluble C5b-9 (SC5b-9). Immunopositivity was detected in association with lamellated bodies in the neuronal cytoplasm, lipofuscin granules, lysosomes and neurofibrillary tangles (NFTs). Such intracellular localization of MAC-like immunoreactive (MAC-LI) staining suggests that neurons remove membrane-inserted MAC fragments by endocytosis. These endocytosed membrane fragments then proceed by retrograde transport to the perikaryon for lysosomal degradation. Attachment to the abnormal cytoskeletal proteins found in neurofibrillary tangles also occurs. The results provide further evidence that complement-mediated injury of neurons plays a part in the pathophysiology of AD.