Clinical Performance of the Elecsys CSF pTau181/Aβ42 Ratio for Concordance with Tau-PET in Two Independent Cohorts
Smith, Ruben LU ; Shaw, Leslie ; Palmqvist, Sebastian LU
; Mattsson-Carlgren, Niklas
LU
; Klein, Gregory
; Tonietto, Matteo
; Quijano-Rubio, Clara
; Rank, Christopher M.
; Andreadou, Myrto
and Burnham, Samantha C.
, et al.
(2025)
In Neurology and Therapy
14(5).
p.2011-2031
- Abstract
Introduction: Amyloid- and tau-positron emission tomography (PET) are promising modalities for detecting pathological changes associated with Alzheimer’s disease (AD); however, their application is limited. Although the use of cerebrospinal fluid (CSF) biomarkers as alternatives to amyloid-PET and tau-PET has been explored, no in vitro diagnostic-approved or commercial CSF biomarker assays are currently available for detecting tau pathology in clinical practice. Methods: In this study, we determined and validated the optimal cutoff value for the ratio of tau phosphorylated at a threonine residue at position 181 (pTau181) to β-amyloid(1–42) (Aβ42) in CSF, measured with the Elecsys® Phospho-Tau (181P) CSF... (More)
Introduction: Amyloid- and tau-positron emission tomography (PET) are promising modalities for detecting pathological changes associated with Alzheimer’s disease (AD); however, their application is limited. Although the use of cerebrospinal fluid (CSF) biomarkers as alternatives to amyloid-PET and tau-PET has been explored, no in vitro diagnostic-approved or commercial CSF biomarker assays are currently available for detecting tau pathology in clinical practice. Methods: In this study, we determined and validated the optimal cutoff value for the ratio of tau phosphorylated at a threonine residue at position 181 (pTau181) to β-amyloid(1–42) (Aβ42) in CSF, measured with the Elecsys® Phospho-Tau (181P) CSF and β-Amyloid(1–42) CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), based on its concordance with binary tau-PET status. Clinical performance was explored using CSF measurements and tau-PET scans retrospectively obtained from a subset of subjects with mild cognitive impairment and dementia due to AD in two independent cohorts, Alzheimer’s Disease Neuroimaging Initiative-2/3 (ADNI-2/3; N = 133) and Swedish BioFINDER-2 (N = 62). Results: In the first part of this analysis (ADNI-2/3 pre-analytics), a CSF pTau181/Aβ42 cutoff value of 0.0395 was selected as the best compromise between positive percent agreement (PPA) and negative percent agreement (NPA) for the tau-PET visual read endpoint. After adjustment to account for differences between the ADNI-specific protocol and the manufacturer’s recommended pre-analytical protocol used in BioFINDER-2, the optimal CSF pTau181/Aβ42 cutoff value was set at 0.037. The adjusted cutoff was validated in BioFINDER-2 and was associated with a PPA of 85.7% (95% confidence interval [CI] 70.6, 93.7), NPA of 70.4% (95% CI 51.5, 84.1), and overall percent agreement (OPA) of 79.0% (95% CI 67.4, 87.3); the positive and negative likelihood ratios were 2.89 and 0.203, respectively. Conclusion: The Elecsys CSF pTau181/Aβ42 ratio may be a reliable tool for identifying tau pathology in clinical practice.
(Less)
- author
- Smith, Ruben
LU
; Shaw, Leslie
; Palmqvist, Sebastian
LU
; Mattsson-Carlgren, Niklas
LU
; Klein, Gregory
; Tonietto, Matteo
; Quijano-Rubio, Clara
; Rank, Christopher M.
; Andreadou, Myrto
and Burnham, Samantha C.
, et al. (More)
- Smith, Ruben
LU
; Shaw, Leslie
; Palmqvist, Sebastian
LU
; Mattsson-Carlgren, Niklas
LU
; Klein, Gregory
; Tonietto, Matteo
; Quijano-Rubio, Clara
; Rank, Christopher M.
; Andreadou, Myrto
; Burnham, Samantha C.
and Stomrud, Erik
LU
(Less)
- author collaboration
- organization
- publishing date
- 2025-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, Cerebrospinal fluid, Clinical performance, Cutoff determination and validation, Elecsys immunoassays, Positron emission tomography, pTau/Aβ, Routine-use pre-analytical handling, Tau pathology
- in
- Neurology and Therapy
- volume
- 14
- issue
- 5
- pages
- 21 pages
- publisher
- Adis
- external identifiers
-
- pmid:40684402
- scopus:105016618124
- ISSN
- 2193-8253
- DOI
- 10.1007/s40120-025-00798-8
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025.
- id
- b81b5c8c-1ac7-42d8-bd0e-1726a646dcf0
- date added to LUP
- 2025-12-09 14:58:19
- date last changed
- 2025-12-10 03:22:16
@article{b81b5c8c-1ac7-42d8-bd0e-1726a646dcf0,
abstract = {{<p>Introduction: Amyloid- and tau-positron emission tomography (PET) are promising modalities for detecting pathological changes associated with Alzheimer’s disease (AD); however, their application is limited. Although the use of cerebrospinal fluid (CSF) biomarkers as alternatives to amyloid-PET and tau-PET has been explored, no in vitro diagnostic-approved or commercial CSF biomarker assays are currently available for detecting tau pathology in clinical practice. Methods: In this study, we determined and validated the optimal cutoff value for the ratio of tau phosphorylated at a threonine residue at position 181 (pTau<sub>181</sub>) to β-amyloid(1–42) (Aβ<sub>42</sub>) in CSF, measured with the Elecsys<sup>®</sup> Phospho-Tau (181P) CSF and β-Amyloid(1–42) CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), based on its concordance with binary tau-PET status. Clinical performance was explored using CSF measurements and tau-PET scans retrospectively obtained from a subset of subjects with mild cognitive impairment and dementia due to AD in two independent cohorts, Alzheimer’s Disease Neuroimaging Initiative-2/3 (ADNI-2/3; N = 133) and Swedish BioFINDER-2 (N = 62). Results: In the first part of this analysis (ADNI-2/3 pre-analytics), a CSF pTau<sub>181</sub>/Aβ<sub>42</sub> cutoff value of 0.0395 was selected as the best compromise between positive percent agreement (PPA) and negative percent agreement (NPA) for the tau-PET visual read endpoint. After adjustment to account for differences between the ADNI-specific protocol and the manufacturer’s recommended pre-analytical protocol used in BioFINDER-2, the optimal CSF pTau<sub>181</sub>/Aβ<sub>42</sub> cutoff value was set at 0.037. The adjusted cutoff was validated in BioFINDER-2 and was associated with a PPA of 85.7% (95% confidence interval [CI] 70.6, 93.7), NPA of 70.4% (95% CI 51.5, 84.1), and overall percent agreement (OPA) of 79.0% (95% CI 67.4, 87.3); the positive and negative likelihood ratios were 2.89 and 0.203, respectively. Conclusion: The Elecsys CSF pTau<sub>181</sub>/Aβ<sub>42</sub> ratio may be a reliable tool for identifying tau pathology in clinical practice.</p>}},
author = {{Smith, Ruben and Shaw, Leslie and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Klein, Gregory and Tonietto, Matteo and Quijano-Rubio, Clara and Rank, Christopher M. and Andreadou, Myrto and Burnham, Samantha C. and Stomrud, Erik}},
issn = {{2193-8253}},
keywords = {{Alzheimer’s disease; Cerebrospinal fluid; Clinical performance; Cutoff determination and validation; Elecsys immunoassays; Positron emission tomography; pTau/Aβ; Routine-use pre-analytical handling; Tau pathology}},
language = {{eng}},
number = {{5}},
pages = {{2011--2031}},
publisher = {{Adis}},
series = {{Neurology and Therapy}},
title = {{Clinical Performance of the Elecsys CSF pTau<sub>181</sub>/Aβ<sub>42</sub> Ratio for Concordance with Tau-PET in Two Independent Cohorts}},
url = {{http://dx.doi.org/10.1007/s40120-025-00798-8}},
doi = {{10.1007/s40120-025-00798-8}},
volume = {{14}},
year = {{2025}},
}