Journal Article

FZJ-2022-03017

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo

Kass, B.FZJ* ; Schemmert, S.FZJ* ; Zafiu, C. ; Pils, M.FZJ* ; Bannach, O.FZJ* ; Kutzsche, J.FZJ* ; Bujnicki, T.FZJ* ; Willbold, D. (Corresponding author)FZJ*

2022
Elsevier Maryland Heights, MO

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Please use a persistent id in citations: http://hdl.handle.net/2128/31676  doi:10.1016/j.xcrm.2022.100630

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.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2022

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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