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@ARTICLE{Albus:904302,
author = {Albus, Alexandra and Kronimus, Yannick and Neumann, Sascha
and Vidovic, Natascha and Frenzel, André and Kuhn, Philipp
and Seifert, Marc and Ziehm, Tamar and van der Wurp, Hendrik
and Dodel, Richard},
title = {{E}ffects of a {M}ultimerized {R}ecombinant {A}utoantibody
{A}gainst {A}myloid-β},
journal = {Neuroscience},
volume = {463},
issn = {0306-4522},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2021-05872},
pages = {355 - 369},
year = {2021},
abstract = {Alzheimer's disease (AD) is the most common
neurodegenerative disease; thus, the search for a cure or
causal therapy has become necessary. Despite intense
research on this topic in recent decades, there is no
curative therapy up today, and also no disease-modifying
treatment has been approved. As promising approach passive
immunization strategies have thereby come forth. In this
study, we focused on naturally occurring autoantibodies
against the AD-associated peptide amyloid-β. These
antibodies have already reported to show beneficial
functions in vitro and in mouse models of AD. However, their
availability is limited due to their low abundance in
peripheral blood. In a recent study, we were able to
generate four recombinant antibodies against amyloid-β. In
the present study, we tested these antibodies in ELISA and
SPR assays for their binding behavior and by aggregation-
and phagocytosis assays as functional evidences to
characterize their amyloid-β-related neutralizing and
clearance abilities. Further ex vivo assay on organotypic
hippocampal slice cultures gave first evidence of microglial
activation and inflammatory features. The tested recombinant
antibodies in IgG format showed, in comparison to naturally
occurring autoantibodies against amyloid-β, insufficient
binding capacities and -affinities. However, after
conversion of one antibody into a single chain format
multimerization of the scFv-Fc construct, the investigated
binding capacity and -affinity showed improvements. Further
functional assays predict a protective effect of this
antibody. Although, all four recombinant antibodies showed
binding to amyloid-β, promising features were only
detectable after conversion into a multimeric format. The
multimeric scFv-Fc antibody exhibited thereby strong impact
on amyloid-β clearance and inhibition of oligomerization.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {33958140},
UT = {WOS:000647661600010},
doi = {10.1016/j.neuroscience.2021.03.006},
url = {https://juser.fz-juelich.de/record/904302},
}