Specific detection of tau seeding activity in Alzheimer's disease using rationally designed biosensor cells.
Alzheimer’s disease
Biosensor cells
Prion-like propagation
Seeding
Tau
Journal
Molecular neurodegeneration
ISSN: 1750-1326
Titre abrégé: Mol Neurodegener
Pays: England
ID NLM: 101266600
Informations de publication
Date de publication:
08 08 2023
08 08 2023
Historique:
received:
09
03
2023
accepted:
28
07
2023
medline:
10
8
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
epublish
Résumé
The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity. We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer's disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer's disease. This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer's disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Sections du résumé
BACKGROUND
The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity.
RESULTS
We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer's disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer's disease.
CONCLUSIONS
This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer's disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Identifiants
pubmed: 37553663
doi: 10.1186/s13024-023-00643-2
pii: 10.1186/s13024-023-00643-2
pmc: PMC10408046
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
53Subventions
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061196
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059789
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058674
Pays : United States
Informations de copyright
© 2023. Editorial Group and BioMed Central Ltd., part of Springer Nature.
Références
PLoS One. 2014 Jun 19;9(6):e100637
pubmed: 24945148
Cell. 2020 Feb 20;180(4):633-644.e12
pubmed: 32032505
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Nat Med. 2020 Aug;26(8):1256-1263
pubmed: 32572268
Acta Neuropathol Commun. 2021 May 26;9(1):99
pubmed: 34039426
Phys Chem Chem Phys. 2016 Aug 3;18(31):21259-68
pubmed: 27250246
Lab Invest. 2021 Dec;101(12):1605-1617
pubmed: 34462532
Neuron. 2021 May 19;109(10):1675-1691.e9
pubmed: 33848474
FASEB J. 2005 May;19(7):869-71
pubmed: 15746184
Front Neurosci. 2018 Apr 24;12:267
pubmed: 29740275
Mol Ther. 2022 Feb 2;30(2):782-797
pubmed: 34563677
Acta Neuropathol. 2017 Jan;133(1):91-100
pubmed: 27878366
Sci Rep. 2015 Aug 20;5:13283
pubmed: 26290434
Neurology. 2003 May 13;60(9):1495-500
pubmed: 12743238
Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4376-85
pubmed: 25261551
Nature. 2017 Jul 13;547(7662):185-190
pubmed: 28678775
Sci Rep. 2017 Sep 20;7(1):11999
pubmed: 28931898
Ann Neurol. 1997 Jan;41(1):17-24
pubmed: 9005861
Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9535-40
pubmed: 23690619
Acta Neuropathol. 2019 Apr;137(4):585-598
pubmed: 30570675
J Biol Chem. 2018 Feb 16;293(7):2408-2421
pubmed: 29259137
Acta Neuropathol. 2001 Jun;101(6):535-9
pubmed: 11515780
J Alzheimers Dis. 2018;64(4):1247-1259
pubmed: 29991132
Elife. 2022 Mar 04;11:
pubmed: 35244536
EMBO J. 2017 Nov 2;36(21):3120-3138
pubmed: 28864542
Nature. 2021 Oct;598(7880):359-363
pubmed: 34588692
Nat Commun. 2015 Oct 13;6:8490
pubmed: 26458742
Sci Transl Med. 2022 Jan 05;14(626):eabg0253
pubmed: 34985969
Acta Neuropathol Commun. 2020 Feb 22;8(1):22
pubmed: 32087764
Brain Commun. 2021 May 04;3(2):fcab096
pubmed: 34222869
J Biol Chem. 2001 Dec 21;276(51):48165-74
pubmed: 11606569
J Biol Chem. 2021 Jan-Jun;296:100715
pubmed: 33930462
Appl Microbiol Biotechnol. 2016 Jan;100(1):215-25
pubmed: 26394862
J Vis Exp. 2015 Dec 08;(106):e53205
pubmed: 26710240
Phys Chem Chem Phys. 2020 Apr 14;22(14):7241-7249
pubmed: 32207466
Genome Res. 2006 Apr;16(4):550-6
pubmed: 16481661
J Biol Chem. 2019 Dec 13;294(50):18952-18966
pubmed: 31578281
J Biol Chem. 2011 Apr 29;286(17):15317-31
pubmed: 21372138
Sci Transl Med. 2020 Jan 1;12(524):
pubmed: 31894103
Front Neurosci. 2020 Nov 04;14:581936
pubmed: 33250706
Neurology. 1992 Mar;42(3 Pt 1):631-9
pubmed: 1549228
EMBO J. 2013 Nov 13;32(22):2920-37
pubmed: 24065130
Cell Rep. 2021 Mar 16;34(11):108843
pubmed: 33730588
Nat Commun. 2019 Jun 7;10(1):2493
pubmed: 31175300
Acta Neuropathol. 2017 May;133(5):751-765
pubmed: 28293793
Cell. 2020 Dec 10;183(6):1699-1713.e13
pubmed: 33188775
Nature. 2020 Apr;580(7803):381-385
pubmed: 32296178
Neuron. 2012 Feb 23;73(4):685-97
pubmed: 22365544
Neurology. 2004 Mar 23;62(6):925-31
pubmed: 15037694
Sci Rep. 2015 Jul 01;5:10270
pubmed: 26130463
Mol Neurodegener. 2020 Jul 16;15(1):39
pubmed: 32677995
J Biol Chem. 2020 Mar 6;295(10):2974-2983
pubmed: 31974166
Ann Neurol. 2016 Sep;80(3):355-67
pubmed: 27351289