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[P2–056]: AN IMMUNOMODULATORY VACCINE AGAINST Aβ FOR ALZHEIMER's DISEASE
Author(s) -
Cao Chuanhai,
Lin Xiaoyang,
Hong Yuzhu,
Ugen Kenneth,
Brown Breanna
Publication year - 2017
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.2017.06.705
Subject(s) - medicine , immune system , antibody , antibody titer , pharmacology , immunology , flow cytometry , monoclonal antibody , titer
protofibrils were readily taken up in human AD-derived microglia in an FcgR-independent manner, while BAN2401 facilitated further uptake of protofibrils in FcgR-mediated fashion. BAN2401 facilitated protofibril uptake in EOC-20 microglia cells was blocked with an FcgR blocker or F(ab’)2 fragments (EC501⁄4257661 ng/mL; corrected for background uptake). Conclusions:Ab can be taken up by microglia via a non-specific pattern-recognizing receptor pathway or through an FcgR-mediated process. Previous work has demonstrated that BAN2401 facilitates protofibril clearance, and this clearance was inhibited by an FcgR blocker to levels lower than those seen in the absence of BAN2401, suggesting a shift from non-specific uptake toward microglial activation and FcgR-dependent microglial phagocytosis. The present studies isolate the FcgR-dependent component of BAN2401-mediated protofibril uptake and provide further support for antibody dependent cellular phagocytosis of Ab protofibrils as the primary mechanism of action for BAN2401.