Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy

外周补体与阿尔茨海默病中淀粉样β肽的相互作用:2. 与淀粉样β肽免疫治疗的关系

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作者:Andrés Crane, William D Brubaker, Jenny U Johansson, Abhishek Trigunaite, Justine Ceballos, Bonnie Bradt, Courtney Glavis-Bloom, Tanya L Wallace, Andrea J Tenner, Joseph Rogers

Discussion

Together with our previous results, showing significant Alzheimer's disease deficits in peripheral Aβ clearance, the present findings strongly suggest that peripheral mechanisms should not be ignored as contributors to the effects of Aβ immunotherapy.

Methods

Multidisciplinary methods were employed to demonstrate enhanced complement-mediated capture of Aβ antibody immune complexes compared with Aβ alone in both erythrocytes and THP1-derived macrophages.

Results

Aβ antibodies dramatically increased complement activation and opsonization of Aβ, followed by commensurately enhanced Aβ capture by human erythrocytes and macrophages. These in vitro findings were consistent with enhanced peripheral clearance of intravenously administered Aβ antibody immune complexes in nonhuman primates.

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