Immune complexes of antibodies with Aβ oligomers cause neuronal death in primary neuronal-glial culture by activating microglia

Abstract

Alzheimer disease (AD) is the most common dementia disorder in the elderly. Recent research suggests that amyloid-contribute to the or a was successful in preclinical studies, however, clinical trials were halted due to brain inflammation, the mechanisms of which are poorly understood. In the present study we aimed to investigate the effects of antigen-antibody complexes formed by and specific monoclonal antibodies in primary neuronal-glial cultures. We found that or by oligomeric virus proteins and their specific antibodies can cause death and loss of neurons. Antibodies bound to -toxic to cultured neurons. The neurotoxicity of antibody-oligomeric antigen complexes was abolished by removal of the Fc region from the antibodies or by removal of microglia from cultures, and was accompanied by inflammatory activation and proliferation of the microglia in culture. In conclusion, immune oligomeric antigens and their specific antibodies exert strong toxic effects on neuronal cells via Fc-dependent microglial activation. Therefore, if endogenous antibodies to oligomeric proteins cross the blood-brain barrier, they may cause neuroinflammation and neurotoxicity. The results suggest that therapies resulting in antibodies to oligomeric oligomeric brain virus proteins should be used with caution or with suppression of microglial activation. This work was supported by the Research Council of Lithuania (grant LIG-04/2012 MALPAMA).