Comparing the Clinical Utility and Diagnostic Performance of Cerebrospinal Fluid P-Tau181, P-Tau217 and P-Tau231 Assays
Leuzy, Antoine LU ; Janelidze, Shorena LU ; Mattsson-Carlgren, Niklas LU
; Palmqvist, Sebastian
LU
; Jacobs, Dirk
; Cicognola, Claudia
LU
; Stomrud, Erik
LU
; Vanmechelen, Eugeen
; Dage, Jeffrey L
and Hansson, Oskar
LU
(2021)
In Neurology
97(17).
p.1681-1694
- Abstract
BACKGROUND AND OBJECTIVES: Phosphorylated tau (P-tau) in cerebrospinal fluid (CSF) is considered an important biomarker in Alzheimer's 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 amyloid-β (Aβ) and Tau positron emission tomography (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: 629 subjects from the Swedish BioFINDER-2 study were... (More)
BACKGROUND AND OBJECTIVES: Phosphorylated tau (P-tau) in cerebrospinal fluid (CSF) is considered an important biomarker in Alzheimer's 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 amyloid-β (Aβ) and Tau positron emission tomography (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: 629 subjects from 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-tau181Lilly, P-tau217Lilly) and P-tau231, we also included P-tau181 measurements from two commonly used assays (Innotest and Elecsys).
RESULTS: Though all P-tau variants increased across the AD continuum, P-tau217Lilly showed the greatest dynamic range (13-fold-increase vs 1.9-5.4-fold-increase for other P-tau variants for AD dementia vs non-AD). P-tau217Lilly showed stronger correlations with Aβ- and Tau-PET (P<0.0001). P-tau217Lilly exhibited higher accuracy than other P-tau variants for separating AD dementia from non-AD (AUC, 0.991vs 0.906-0.982, P<0.0001) and for identifying Aβ- (AUC, 0.951 vs 0.816-0.924, P<0.0001) and Tau-PET positivity (AUC, 0.957 vs 0.836-0.938, P<0.0001). Finally, P-tau181Lilly generally performed better than the other P-tau181 assays, (e.g., AD dementia vs non-AD, AUC, 0.976 vs 0.923, P<0.0001).
DISCUSSION: CSF P-tau217Lilly seem to be more useful than other included P-tau assays in the work-up of AD. Varied results across P-tau181 assays also highlights the importance of anti-tau antibodies for biomarker performance.
CLASSIFICATION OF EVIDENCE: This study provides class II evidence that phosphorylated tau at threonine 217 provides higher diagnostic accuracy for diagnosis of AD dementia than P-tau at threonine 181 or 231.
(Less)
- author
- Leuzy, Antoine
LU
; Janelidze, Shorena
LU
; Mattsson-Carlgren, Niklas
LU
; Palmqvist, Sebastian
LU
; Jacobs, Dirk
; Cicognola, Claudia
LU
; Stomrud, Erik
LU
; Vanmechelen, Eugeen
; Dage, Jeffrey L
and Hansson, Oskar
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurology
- volume
- 97
- issue
- 17
- pages
- 1681 - 1694
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85120834369
- pmid:34493616
- ISSN
- 1526-632X
- DOI
- 10.1212/WNL.0000000000012727
- language
- English
- LU publication?
- yes
- id
- 0b37ddf2-225f-4cb0-9bfe-45af0bb3a798
- date added to LUP
- 2021-09-20 13:35:22
- date last changed
- 2024-06-18 06:03:45
@article{0b37ddf2-225f-4cb0-9bfe-45af0bb3a798,
abstract = {{<p>BACKGROUND AND OBJECTIVES: Phosphorylated tau (P-tau) in cerebrospinal fluid (CSF) is considered an important biomarker in Alzheimer's 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 amyloid-β (Aβ) and Tau positron emission tomography (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.</p><p>METHODS: 629 subjects from 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-tau181Lilly, P-tau217Lilly) and P-tau231, we also included P-tau181 measurements from two commonly used assays (Innotest and Elecsys).</p><p>RESULTS: Though all P-tau variants increased across the AD continuum, P-tau217Lilly showed the greatest dynamic range (13-fold-increase vs 1.9-5.4-fold-increase for other P-tau variants for AD dementia vs non-AD). P-tau217Lilly showed stronger correlations with Aβ- and Tau-PET (P<0.0001). P-tau217Lilly exhibited higher accuracy than other P-tau variants for separating AD dementia from non-AD (AUC, 0.991vs 0.906-0.982, P<0.0001) and for identifying Aβ- (AUC, 0.951 vs 0.816-0.924, P<0.0001) and Tau-PET positivity (AUC, 0.957 vs 0.836-0.938, P<0.0001). Finally, P-tau181Lilly generally performed better than the other P-tau181 assays, (e.g., AD dementia vs non-AD, AUC, 0.976 vs 0.923, P<0.0001).</p><p>DISCUSSION: CSF P-tau217Lilly seem to be more useful than other included P-tau assays in the work-up of AD. Varied results across P-tau181 assays also highlights the importance of anti-tau antibodies for biomarker performance.</p><p>CLASSIFICATION OF EVIDENCE: This study provides class II evidence that phosphorylated tau at threonine 217 provides higher diagnostic accuracy for diagnosis of AD dementia than P-tau at threonine 181 or 231.</p>}},
author = {{Leuzy, Antoine and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Jacobs, Dirk and Cicognola, Claudia and Stomrud, Erik and Vanmechelen, Eugeen and Dage, Jeffrey L and Hansson, Oskar}},
issn = {{1526-632X}},
language = {{eng}},
number = {{17}},
pages = {{1681--1694}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology}},
title = {{Comparing the Clinical Utility and Diagnostic Performance of Cerebrospinal Fluid P-Tau181, P-Tau217 and P-Tau231 Assays}},
url = {{http://dx.doi.org/10.1212/WNL.0000000000012727}},
doi = {{10.1212/WNL.0000000000012727}},
volume = {{97}},
year = {{2021}},
}