Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
received:
16
01
2021
accepted:
19
08
2021
pubmed:
9
9
2021
medline:
30
10
2021
entrez:
8
9
2021
Statut:
ppublish
Résumé
Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including p-tau at threonines 181 (p-tau181), 217 (p-tau217), and 231 (p-tau231). However, no studies have compared their diagnostic performance or association to β-amyloid (Aβ) and tau-PET. Understanding which p-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of p-tau181, p-tau217, and p-tau231 in CSF for AD and their association with Aβ and tau-PET. A total of 629 participants in the Swedish BioFINDER-2 study were included (cognitively unimpaired, n = 334; Aβ-positive mild cognitive impairment, n = 84; AD dementia, n = 119; and non-AD disorders, n = 92). In addition to p-tau181 and p-tau217 measured using assays with the same detector antibodies from Eli Lilly (p-tau181 Although all p-tau variants increased across the AD continuum, p-tau217 CSF p-tau217 This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.
Sections du résumé
BACKGROUND AND OBJECTIVES
Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including p-tau at threonines 181 (p-tau181), 217 (p-tau217), and 231 (p-tau231). However, no studies have compared their diagnostic performance or association to β-amyloid (Aβ) and tau-PET. Understanding which p-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of p-tau181, p-tau217, and p-tau231 in CSF for AD and their association with Aβ and tau-PET.
METHODS
A total of 629 participants in the Swedish BioFINDER-2 study were included (cognitively unimpaired, n = 334; Aβ-positive mild cognitive impairment, n = 84; AD dementia, n = 119; and non-AD disorders, n = 92). In addition to p-tau181 and p-tau217 measured using assays with the same detector antibodies from Eli Lilly (p-tau181
RESULTS
Although all p-tau variants increased across the AD continuum, p-tau217
DISCUSSION
CSF p-tau217
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.
Identifiants
pubmed: 34493616
pii: WNL.0000000000012727
doi: 10.1212/WNL.0000000000012727
pmc: PMC8605616
doi:
Substances chimiques
Biomarkers
0
MAPT protein, human
0
Protein Isoforms
0
tau Proteins
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1681-e1694Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Brain. 2011 Sep;134(Pt 9):2456-77
pubmed: 21810890
Ann Neurol. 2013 Aug;74(2):199-208
pubmed: 23686697
Sci Adv. 2020 Apr 15;6(16):eaaz2387
pubmed: 32426454
JAMA Neurol. 2014 Oct;71(10):1282-9
pubmed: 25155658
PLoS One. 2013 Oct 07;8(10):e76523
pubmed: 24116116
Neurology. 1993 Feb;43(2):250-60
pubmed: 8094895
J Nucl Med. 2013 Aug;54(8):1472-8
pubmed: 23740104
PLoS One. 2015 Apr 02;10(3):e0121945
pubmed: 25835001
Mol Chem Neuropathol. 1995 Dec;26(3):231-45
pubmed: 8748926
Front Aging Neurosci. 2019 May 21;11:121
pubmed: 31178717
Brain. 2007 Oct;130(Pt 10):e82
pubmed: 17615094
Ann Neurol. 2016 Aug;80(2):247-58
pubmed: 27323247
Trends Pharmacol Sci. 2015 May;36(5):297-309
pubmed: 25840462
Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):342-354
pubmed: 31612245
Mov Disord. 2017 Jun;32(6):853-864
pubmed: 28467028
Brain. 2006 Nov;129(Pt 11):3035-41
pubmed: 17012293
Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5
pubmed: 3131773
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Alzheimers Dement. 2018 Nov;14(11):1470-1481
pubmed: 29499171
Lancet Neurol. 2003 Oct;2(10):605-13
pubmed: 14505582
Lancet Neurol. 2016 May;15(6):546-8
pubmed: 27302120
Alzheimers Dement. 2021 May;17(5):755-767
pubmed: 33252199
Lancet Neurol. 2006 Mar;5(3):228-34
pubmed: 16488378
J Proteome Res. 2016 Feb 5;15(2):667-76
pubmed: 26742856
Neurobiol Aging. 1998 Jul-Aug;19(4):287-96
pubmed: 9733160
Lancet Neurol. 2016 Jun;15(7):673-684
pubmed: 27068280
Anal Chem. 2016 Apr 5;88(7):3704-14
pubmed: 26877193
J Nucl Med. 2020 Dec;61(12):1820-1824
pubmed: 32358089
Expert Rev Neurother. 2015 Jan;15(1):115-22
pubmed: 25555397
Brain. 2015 Sep;138(Pt 9):2716-31
pubmed: 26133663
J Neurosci. 2015 Jul 29;35(30):10851-65
pubmed: 26224867
Neurology. 2013 Jan 29;80(5):496-503
pubmed: 23359374
Acta Neuropathol Commun. 2020 Aug 27;8(1):149
pubmed: 32854776
Neurology. 2018 Oct 2;91(14):e1295-e1306
pubmed: 30217935
Nat Commun. 2020 Apr 3;11(1):1683
pubmed: 32246036
Acta Neuropathol. 2013 Aug;126(2):303-6
pubmed: 23824268
Ann Neurol. 2011 Jan;69(1):181-92
pubmed: 21280088
Sci Transl Med. 2017 Apr 19;9(386):
pubmed: 28424326
Neuron. 2018 Mar 21;97(6):1284-1298.e7
pubmed: 29566794
Acta Neuropathol. 2019 Feb;137(2):279-296
pubmed: 30547227
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
Alzheimers Dement. 2017 Mar;13(3):205-216
pubmed: 27697430
JAMA Neurol. 2020 Aug 1;77(8):955-965
pubmed: 32391858
Cell. 2020 Dec 10;183(6):1699-1713.e13
pubmed: 33188775
Trends Pharmacol Sci. 1991 Oct;12(10):383-8
pubmed: 1763432
Biometrics. 1988 Sep;44(3):837-45
pubmed: 3203132
Nat Med. 2020 Mar;26(3):398-407
pubmed: 32161412