Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo.
amyloid beta oligomer quantitation
brain homogenates
d-enantiomeric peptides
ex vivo target engagement
sFIDA
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
17 05 2022
17 05 2022
Historique:
received:
08
12
2021
revised:
28
02
2022
accepted:
15
04
2022
entrez:
18
5
2022
pubmed:
19
5
2022
medline:
21
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35584626
pii: S2666-3791(22)00155-0
doi: 10.1016/j.xcrm.2022.100630
pmc: PMC9133466
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100630Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.W. is a founder and shareholder of the company Priavoid and member of its supervisory board. D.W. is co-inventor of patents related to the compound RD2. C.Z., D.W., and B.K. are inventors of patent WO2019101250A1 (method for quantifying protein aggregates of a protein misfolding disease in a sample). D.W., O.B., and C.Z. are founders and shareholders of attyloid. D.W. is member of attyloid’s supervisory board. These had no influence on the interpretation of the data. All other authors declare no competing interests.
Références
Molecules. 2017 Oct 10;22(10):
pubmed: 28994710
PLoS One. 2012;7(8):e42823
pubmed: 22912745
Nucl Med Biol. 2012 Apr;39(3):315-23
pubmed: 22136889
ChemMedChem. 2009 Feb;4(2):276-82
pubmed: 19072935
J Biol Chem. 2004 Nov 12;279(46):47497-505
pubmed: 15322133
Neurobiol Aging. 2011 Dec;32(12):2324.e1-6
pubmed: 20970889
Nat Med. 1997 Jul;3(7):756-60
pubmed: 9212102
Eur J Neurosci. 2004 Oct;20(7):1945-52
pubmed: 15380017
ACS Chem Neurosci. 2010 Sep 15;1(9):639-48
pubmed: 22778851
Clin Chim Acta. 2017 Mar;466:152-159
pubmed: 28088342
J Neurochem. 2009 Dec;111(6):1369-82
pubmed: 19804379
Acta Neuropathol. 2015 Feb;129(2):167-82
pubmed: 25534025
Am J Pathol. 2005 Aug;167(2):505-15
pubmed: 16049335
Alzheimers Dement. 2020 Mar 10;:
pubmed: 32157811
Alzheimers Res Ther. 2020 Jun 13;12(1):74
pubmed: 32534594
Neurochem Int. 2012 Jan;60(2):153-62
pubmed: 22100791
Sci Rep. 2017 Nov 24;7(1):16275
pubmed: 29176708
Eur J Pharm Sci. 2018 Mar 1;114:93-102
pubmed: 29225107
Acta Neuropathol. 2018 Jul;136(1):19-40
pubmed: 29687257
PLoS One. 2012;7(2):e32014
pubmed: 22355408
Chembiochem. 2003 Sep 5;4(9):811-5
pubmed: 12964153
Nat Neurosci. 2012 Jan 29;15(3):349-57
pubmed: 22286176
Science. 1990 Jun 1;248(4959):1124-6
pubmed: 2111584
Science. 2016 May 6;352(6286):712-716
pubmed: 27033548
Curr Med Chem. 2014;21(12):1448-57
pubmed: 24304283
J Alzheimers Dis. 2013;34(3):609-20
pubmed: 23271316
Nature. 2002 Apr 4;416(6880):535-9
pubmed: 11932745
Ann Neurol. 2001 Jun;49(6):697-705
pubmed: 11409420
Mol Neurobiol. 2019 Mar;56(3):2211-2223
pubmed: 30003517
Neurobiol Dis. 2006 Dec;24(3):516-24
pubmed: 17029828
FEBS Lett. 2018 Feb;592(4):516-534
pubmed: 29360176
Neurobiol Dis. 2019 Apr;124:36-45
pubmed: 30391539
Front Mol Neurosci. 2019 Jul 31;12:176
pubmed: 31417354
Biomol Eng. 2001 Jun;17(6):157-65
pubmed: 11337275
Alzheimers Dement. 2015 Nov;11(11):1286-305
pubmed: 25846299
Chembiochem. 2003 Aug 4;4(8):748-53
pubmed: 12898626
J Neurosci. 2017 Jan 4;37(1):152-163
pubmed: 28053038
Alzheimers Dement (N Y). 2020 Mar 20;6(1):e12001
pubmed: 32211506
Neurosci Lett. 2005 Dec 23;390(2):87-92
pubmed: 16169151
ChemMedChem. 2008 Dec;3(12):1848-52
pubmed: 19016284
Neuropsychopharmacology. 2010 Mar;35(4):870-80
pubmed: 20010553
PLoS One. 2012;7(7):e41457
pubmed: 22848501
Eur J Pharm Sci. 2016 Jun 30;89:31-8
pubmed: 27086111
Mol Biosyst. 2009 Aug;5(8):783-6
pubmed: 19603110
J Cell Mol Med. 2012 Feb;16(2):287-95
pubmed: 21418518
Biol Chem. 2017 Apr 1;398(4):465-475
pubmed: 27811340
ACS Chem Neurosci. 2018 Nov 21;9(11):2679-2688
pubmed: 29893543
Front Neurol. 2020 Feb 25;11:108
pubmed: 32158425
Sci Rep. 2015 Sep 23;5:13222
pubmed: 26394756
Nat Commun. 2016 Mar 24;7:10948
pubmed: 27009901
J Neurochem. 2008 May;105(3):584-94
pubmed: 18042177
J Biol Chem. 1999 Mar 5;274(10):6483-92
pubmed: 10037741
Nature. 2018 Mar 1;555(7694):61-66
pubmed: 29466338
J Alzheimers Dis. 2013;34(4):985-94
pubmed: 23313925
ACS Chem Neurosci. 2019 Dec 18;10(12):4800-4809
pubmed: 31710458
Pharm Res. 2016 Feb;33(2):328-36
pubmed: 26381279
J Alzheimers Dis. 2016 Jul 27;54(1):79-88
pubmed: 27472876
Am J Pathol. 2000 Oct;157(4):1283-98
pubmed: 11021833
Alzheimers Dement. 2011 May;7(3):280-92
pubmed: 21514248
Hum Mol Genet. 2004 Jan 15;13(2):159-70
pubmed: 14645205
Sci Rep. 2019 Apr 5;9(1):5715
pubmed: 30952881
Genet Anal. 1996 Dec;13(6):159-63
pubmed: 9117892
J Biol Chem. 2004 May 7;279(19):20296-306
pubmed: 14985348
Vet Microbiol. 2007 Aug 31;123(4):294-304
pubmed: 17499942