Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Aβ pathology are detected.
Alzheimer’s disease
biomarker
cerebrospinal fluid
plasma
tau
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 12 2020
07 12 2020
Historique:
received:
11
06
2020
revised:
09
09
2020
accepted:
09
09
2020
pubmed:
11
11
2020
medline:
21
7
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
In Alzheimer's disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer's continuum. We measured three novel CSF p-tau biomarkers, phosphorylated at threonine-181 and threonine-217 with an N-terminal partner antibody and at threonine-231 with a mid-region partner antibody. These were compared with an automated mid-region p-tau181 assay (Elecsys) as the gold standard p-tau measure. We demonstrate that these novel p-tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid-β (Aβ) pathology are detected, and can accurately differentiate Aβ-positive from Aβ-negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N-terminal p-tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p-tau assays.
Identifiants
pubmed: 33169916
doi: 10.15252/emmm.202012921
pmc: PMC7721364
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12921Subventions
Organisme : "la Caixa" Foundation ("la Caixa")
ID : LCF/PR/GN17/50300004
Organisme : Alzheimer's Association (AA)
ID : TriBEKa-17-519007
Organisme : Catalan Government
ID : 2017-SGR-892
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (MSCA)
ID : 752310
Organisme : BrightFocus Foundation (BFF)
ID : A2020812F
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : 681712
Organisme : Swedish State Support for Clinical Research
ID : ALFGBG-720931
Organisme : ALF-agreement
ID : ALFGBG-715986
Organisme : EU Joint Programme - Neurodegenerative Disease Research (JPND)
ID : JPND2019-466-236
Organisme : MEC | Instituto de Salud Carlos III (ISCIII)
ID : PI19/00155
Organisme : MEC | Instituto de Salud Carlos III (ISCIII)
ID : CP II 17/00029
Organisme : Ministerio de Ciencia, Innovación y Universidades (MCIU)
ID : IJC2018-037478-I
Organisme : Ministerio de Ciencia, Innovación y Universidades (MCIU)
ID : FJCI-2017-33437
Organisme : Ministerio de Ciencia, Innovación y Universidades (MCIU)
ID : RYC2018-026053-I
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : RYC-2013-13054
Organisme : Ministerio de Economía y Competitividad (MEC)
ID : IEDI-2016-00690
Organisme : Svenska Forskningsrådet Formas
ID : 2018-02532
Organisme : Svenska Forskningsrådet Formas
ID : 2017-00915
Organisme : Swedish Alzheimer Foundation
ID : AF-930627
Organisme : Swedish Alzheimer Foundation
ID : AF-742881
Organisme : Alzheimer's Drug Discovery Foundation (ADDF)
ID : 201809-2016862
Organisme : Alzheimer's Drug Discovery Foundation (ADDF)
ID : RDAPB-201809-2016615
Organisme : Hjärnfonden Sweden
ID : FO2017-0243
Investigateurs
Annabella Beteta
(A)
Raffaele Cacciaglia
(R)
Alba Cañas
(A)
Carme Deulofeu
(C)
Irene Cumplido
(I)
Ruth Dominguez
(R)
Maria Emilio
(M)
Carles Falcon
(C)
Sherezade Fuentes
(S)
Laura Hernandez
(L)
Gema Huesa
(G)
Jordi Huguet
(J)
Paula Marne
(P)
Tania Menchón
(T)
Grégory Operto
(G)
Albina Polo
(A)
Sandra Pradas
(S)
Anna Soteras
(A)
Marc Vilanova
(M)
Natalia Vilor-Tejedor
(N)
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Am J Pathol. 2002 Apr;160(4):1269-78
pubmed: 11943712
Alzheimers Dement. 2019 Apr;15(4):570-580
pubmed: 30639421
Acta Neuropathol Commun. 2019 Dec 3;7(1):192
pubmed: 31796124
JAMA Neurol. 2019 May 1;76(5):542-551
pubmed: 30715078
Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5
pubmed: 3131773
EMBO Mol Med. 2017 Sep;9(9):1212-1223
pubmed: 28743782
Neurosci Lett. 1999 Jul 30;270(2):91-4
pubmed: 10462105
Brain Behav. 2018 Nov;8(11):e01128
pubmed: 30329219
Ann Neurol. 2017 Jan;81(1):117-128
pubmed: 27997036
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Nat Rev Neurol. 2018 Aug;14(8):457-469
pubmed: 29985474
Neurology. 2002 Aug 27;59(4):627-9
pubmed: 12196665
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32725127
Lancet Neurol. 2006 Mar;5(3):228-34
pubmed: 16488378
J Neuropathol Exp Neurol. 2016 Jun 12;75(8):748-754
pubmed: 27297671
Neurology. 2016 Aug 30;87(9):920-6
pubmed: 27473132
J Proteome Res. 2016 Feb 5;15(2):667-76
pubmed: 26742856
J Biol Chem. 2012 Dec 14;287(51):42751-62
pubmed: 23105105
Lancet Neurol. 2016 Jun;15(7):673-684
pubmed: 27068280
J Alzheimers Dis. 2013;34(2):457-68
pubmed: 23234879
J Neuropathol Exp Neurol. 2012 May;71(5):362-81
pubmed: 22487856
Ann Neurol. 1997 Jan;41(1):17-24
pubmed: 9005861
JAMA. 2020 Aug 25;324(8):772-781
pubmed: 32722745
Alzheimers Dement. 2015 Jan;11(1):1-15.e1-4
pubmed: 25443857
Annu Rev Neurosci. 2001;24:1121-59
pubmed: 11520930
Clin Biochem. 2019 Oct;72:30-38
pubmed: 31129184
Arch Neurol. 2005 May;62(5):770-3
pubmed: 15883264
Nat Rev Neurol. 2010 Mar;6(3):131-44
pubmed: 20157306
J Biol Chem. 2012 Feb 3;287(6):3842-9
pubmed: 22057275
Ann Neurol. 2013 Aug;74(2):199-208
pubmed: 23686697
Neurosci Lett. 2000 May 5;285(1):49-52
pubmed: 10788705
Alzheimers Dement. 2019 Mar;15(3):487-496
pubmed: 30419228
Sci Adv. 2020 Apr 15;6(16):eaaz2387
pubmed: 32426454
EMBO Rep. 2013 Apr;14(4):389-94
pubmed: 23412472
Brain. 2019 Oct 1;142(10):3230-3242
pubmed: 31501889
J Alzheimers Dis. 2015;49(1):93-100
pubmed: 26444757
Mol Cell Neurosci. 2019 Jun;97:18-33
pubmed: 30529601
Alzheimers Dement. 2019 Feb;15(2):205-216
pubmed: 30347188
Biochem J. 1994 Aug 1;301 ( Pt 3):871-7
pubmed: 7519852
PLoS One. 2013 Oct 07;8(10):e76523
pubmed: 24116116
Ann Neurol. 2009 Apr;65(4):403-13
pubmed: 19296504
Mol Neurodegener. 2017 Nov 21;12(1):87
pubmed: 29157277
J Neurosci. 2015 Jul 29;35(30):10851-65
pubmed: 26224867
JAMA Neurol. 2018 May 1;75(5):548-556
pubmed: 29435558
Exp Neurol. 2000 Nov;166(1):201-3
pubmed: 11031097
Alzheimers Res Ther. 2020 Mar 4;12(1):22
pubmed: 32131891
J Biol Chem. 1988 Jun 15;263(17):7948-53
pubmed: 3131334
Brain. 2016 Aug;139(Pt 8):2249-60
pubmed: 27286736
Neurology. 2018 Oct 2;91(14):e1295-e1306
pubmed: 30217935
Nat Commun. 2020 Apr 3;11(1):1683
pubmed: 32246036
Mol Neurobiol. 2001 Aug-Dec;24(1-3):87-97
pubmed: 11831556
Arch Gen Psychiatry. 2004 Jan;61(1):95-102
pubmed: 14706948
Arch Neurol. 2002 Aug;59(8):1267-72
pubmed: 12164722
FEBS Lett. 2012 Jan 2;586(1):47-54
pubmed: 22138183
Alzheimers Dement. 2016 Mar;12(3):292-323
pubmed: 27012484
Acta Neuropathol Commun. 2016 Jun 13;4(1):58
pubmed: 27296779
Nat Med. 2020 Mar;26(3):387-397
pubmed: 32123386
Sci Transl Med. 2014 Mar 5;6(226):226ra30
pubmed: 24598588
Alzheimers Dement. 2019 Jun;15(6):742-753
pubmed: 30967340
JAMA. 2009 Jul 22;302(4):385-93
pubmed: 19622817
Neurobiol Aging. 2009 May;30(5):672-81
pubmed: 17920160
Brain. 2019 Apr 1;142(4):1063-1076
pubmed: 30753379
Neurobiol Dis. 2012 Dec;48(3):356-66
pubmed: 22668776
Neurosci Lett. 2002 Nov 29;333(3):183-6
pubmed: 12429378
Science. 1991 Feb 8;251(4994):675-8
pubmed: 1899488
Sci Transl Med. 2013 Jul 17;5(194):194re2
pubmed: 23863834
PLoS One. 2012;7(5):e36873
pubmed: 22615831
Alzheimers Res Ther. 2019 Mar 21;11(1):27
pubmed: 30902090
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Neuron. 2018 Mar 21;97(6):1284-1298.e7
pubmed: 29566794
Exp Gerontol. 2009 Sep;44(9):579-85
pubmed: 19539742
Neurosci Lett. 2000 Jun 30;287(3):187-90
pubmed: 10863026
Alzheimers Dement. 2020 Oct;16(10):1358-1371
pubmed: 32573951
N Engl J Med. 2012 Aug 30;367(9):795-804
pubmed: 22784036
Neurology. 2018 Aug 28;91(9):e859-e866
pubmed: 30068637
J Alzheimers Dis. 2005 Sep;8(1):29-41
pubmed: 16155347
Alzheimers Dement. 2018 Aug;14(8):989-997
pubmed: 29626426
Acta Neuropathol. 2019 Feb;137(2):279-296
pubmed: 30547227
Ann Neurol. 2016 Jan;79(1):110-9
pubmed: 26505746
Nat Med. 2020 Mar;26(3):379-386
pubmed: 32123385
Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
pubmed: 3088567
EMBO Mol Med. 2020 Dec 7;12(12):e12921
pubmed: 33169916
J Neurosci. 2004 Sep 8;24(36):7895-902
pubmed: 15356202
Alzheimers Dement. 2018 Jul;14(7):869-879
pubmed: 29580670
Neuron. 1989 Oct;3(4):519-26
pubmed: 2484340
Dement Geriatr Cogn Dis Extra. 2016 Jul 15;6(2):283-94
pubmed: 27504117
Alzheimers Res Ther. 2020 Mar 17;12(1):26
pubmed: 32183883
Brain. 2016 Sep;139(Pt 9):2540-53
pubmed: 27401520
J Neural Transm (Vienna). 2019 Mar;126(3):339-348
pubmed: 30767082
J Alzheimers Dis. 2007 Dec;12(4):365-75
pubmed: 18198423
FEBS Lett. 2010 Jul 16;584(14):3085-8
pubmed: 20553717
Sci Transl Med. 2016 May 11;8(338):338ra66
pubmed: 27169802
Mol Chem Neuropathol. 1995 Dec;26(3):231-45
pubmed: 8748926
Anal Bioanal Chem. 2009 Dec;395(7):2263-7
pubmed: 19821112
Alzheimers Dement (N Y). 2016 Mar 03;2(2):82-92
pubmed: 29067295
Lancet Neurol. 2020 May;19(5):422-433
pubmed: 32333900
Shanghai Arch Psychiatry. 2016 Oct 25;28(5):271-279
pubmed: 28638201
J Alzheimers Dis. 2016 Nov 1;55(1):303-313
pubmed: 27636850
Front Aging Neurosci. 2014 Oct 16;6:287
pubmed: 25360114
Acta Neuropathol. 2002 Jan;103(1):26-35
pubmed: 11837744
Neurology. 2013 May 7;80(19):1784-91
pubmed: 23576620
Alzheimers Dement. 2019 May;15(5):655-665
pubmed: 30846386
Nat Med. 2020 Mar;26(3):398-407
pubmed: 32161412
Eur J Nucl Med Mol Imaging. 2017 Nov;44(12):2053-2059
pubmed: 28643043
Front Aging Neurosci. 2019 May 21;11:121
pubmed: 31178717
CNS Neurosci Ther. 2018 Aug;24(8):734-740
pubmed: 29453935
Mol Neurodegener. 2017 Sep 4;12(1):63
pubmed: 28866979
Acta Neuropathol. 2013 Nov;126(5):659-70
pubmed: 23812320
Front Neurol. 2015 Aug 19;6:179
pubmed: 26347708