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@ARTICLE{Kass:909117,
author = {Kass, Bettina and Schemmert, Sarah and Zafiu, Christian and
Pils, Marlene and Bannach, Oliver and Kutzsche, Janine and
Bujnicki, Tuyen and Willbold, Dieter},
title = {{A}β oligomer concentration in mouse and human brain and
its drug-induced reduction ex vivo},
journal = {Cell reports / Medicine},
volume = {3},
number = {5},
issn = {2666-3791},
address = {Maryland Heights, MO},
publisher = {Elsevier},
reportid = {FZJ-2022-03017},
pages = {100630 -},
year = {2022},
abstract = {The elimination of amyloid beta (Aβ) oligomers is a
promising strategy for therapeutic drug development of
Alzheimer’s disease (AD). AD mouse models that develop Aβ
pathology have been used to demonstrate in vivo efficacy of
compounds that later failed in clinical development. Here,
we analyze the concentration and size distribution of Aβ
oligomers in different transgenic mouse models of AD and in
human brain samples by surface-based fluorescence intensity
distribution analysis (sFIDA), a highly sensitive method for
detecting and quantitating protein aggregates. We
demonstrate dose- and time-dependent oligomer elimination by
the compound RD2 in mouse and human AD brain homogenates as
sources of native Aβ oligomers. Such ex vivo target
engagement analyses with mouse- and human-brain-derived
oligomers have the potential to enhance the translational
value from pre-clinical proof-of-concept studies to clinical
trials.},
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 = {35584626},
UT = {WOS:000830992600003},
doi = {10.1016/j.xcrm.2022.100630},
url = {https://juser.fz-juelich.de/record/909117},
}