Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation

Monika Zilkova*, Anna Nolle, Branislav Kovacech, Eva Kontsekova, Petronela Weisova, Peter Filipcik, Rostislav Skrabana, Michal Prcina, Tomas Hromadka, Ondrej Cehlar, Gabriela Paulikova Rolkova, Denisa Maderova, Michal Novak, Norbert Zilka, Jeroen J.M. Hoozemans

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Immunotherapies targeting pathological tau have recently emerged as a promising approach for treatment of neurodegenerative disorders. We have previously showed that the mouse antibody DC8E8 discriminates between healthy and pathological tau, reduces tau pathology in murine tauopathy models and inhibits neuronal internalization of AD tau species in vitro. Here we show, that DC8E8 and antibodies elicited against the first-in-man tau vaccine, AADvac1, which is based on the DC8E8 epitope peptide, both promote uptake of pathological tau by mouse primary microglia. IgG1 and IgG4 isotypes of AX004, the humanized versions of DC8E8, accelerate tau uptake by human primary microglia isolated from post-mortem aged and diseased brains. This promoting activity requires the presence of the Fc-domain of the antibodies. The IgG1 isotype of AX004 showed greater ability to promote tau uptake compared to the IgG4 isotype, while none of the antibody-tau complexes provoked increased pro-inflammatory activity of microglia. Our data suggest that IgG1 has better suitability for therapeutic development.

Original languageEnglish
Article number74
JournalActa neuropathologica communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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