TY  - JOUR
AU  - Kass, Bettina
AU  - Schemmert, Sarah
AU  - Zafiu, Christian
AU  - Pils, Marlene
AU  - Bannach, Oliver
AU  - Kutzsche, Janine
AU  - Bujnicki, Tuyen
AU  - Willbold, Dieter
TI  - Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo
JO  - Cell reports / Medicine
VL  - 3
IS  - 5
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - FZJ-2022-03017
SP  - 100630 -
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 35584626
UR  - <Go to ISI:>//WOS:000830992600003
DO  - DOI:10.1016/j.xcrm.2022.100630
UR  - https://juser.fz-juelich.de/record/909117
ER  -