Complement activation in acquired and hereditary amyloid neuropathy

The pathogenesis of the axonal degeneration in acquired or hereditary amylo idosis is unknown. In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. Complement activation p roducts were detected on and around amyloid deposits within peripheral nerv es. We found no difference in the extent, location or pattern of complement activation products between the 2 forms of amyloidosis. The presence of ea rly classical pathway activation markers in the absence of antibody in here ditary cases suggests an antibody-independent activation of the classical p athway through binding of C1q. The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. The detection of C5b -9 neoantigen on amyloid deposits demonstrated that the full complement cas cade was activated. Complement activation on amyloid deposits and the gener ation of C5b-9 in vivo may contribute to bystander injury of axons in the v icinity of amyloid deposits.