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Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy
Author(s) -
Crane Andrés,
Brubaker William D.,
Johansson Jenny U.,
Trigunaite Abhishek,
Ceballos Justine,
Bradt Bonnie,
GlavisBloom Courtney,
Wallace Tanya L.,
Tenner Andrea J.,
Rogers Joseph
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.04.015
Subject(s) - antibody opsonization , antibody , immunotherapy , immune system , immunology , complement receptor 1 , complement system , amyloid (mycology) , immune complex , peptide , peripheral , medicine , chemistry , pathology , opsonin , biochemistry
Our previous studies have shown that amyloid β peptide (Aβ) is subject to complement‐mediated clearance from the peripheral circulation, and that this mechanism is deficient in Alzheimer's disease. The mechanism should be enhanced by Aβ antibodies that form immune complexes (ICs) with Aβ, and therefore may be relevant to current Aβ immunotherapy approaches. 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. 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.