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Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease

Blennow, Kaj LU ; Stomrud, Erik LU orcid ; Zetterberg, Henrik LU ; Borlinghaus, Niels ; Corradini, Veronika ; Manuilova, Ekaterina ; Müller-Hübner, Laura ; Quevenco, Frances Catherine ; Rutz, Sandra and Hansson, Oskar LU orcid (2023) In Clinical Chemistry and Laboratory Medicine 61(2). p.234-244
Abstract

Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys® CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine. Analytical performance was assessed using CSF samples measured with Elecsys CSF Gen II immunoassays on cobas e analyzers. Aβ42 Gen I/Gen II immunoassay method comparisons were performed (Passing-Bablok regression). Cut-off values were adjusted using estimated bias in biomarker levels between BioFINDER protocol aliquots/Gen I immunoassays and Gen... (More)

Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys® CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine. Analytical performance was assessed using CSF samples measured with Elecsys CSF Gen II immunoassays on cobas e analyzers. Aβ42 Gen I/Gen II immunoassay method comparisons were performed (Passing-Bablok regression). Cut-off values were adjusted using estimated bias in biomarker levels between BioFINDER protocol aliquots/Gen I immunoassays and Gen II protocol aliquots/immunoassays. Distribution of Gen II immunoassay values was evaluated in AD, mild cognitive impairment (MCI), and cognitively normal cohorts; percentage observations outside the measuring range were derived. The Gen II immunoassays demonstrated good analytical performance, including repeatability, intermediate precision, lot-to-lot agreement (Pearson's r: ≥0.999), and platform agreement (Pearson's r: ≥0.995). Aβ42 Gen I/Gen II immunoassay measurements were strongly correlated (Pearson's r: 0.985-0.999). Aβ42 Gen II immunoassay cut-offs were adjusted to 1,030 and 800 ng/L, and pTau181/Aβ42 ratio cut-offs to 0.023 and 0.029, for Gen II and I protocols, respectively. No observations were below the lower limit of the measuring range; above the upper limit, there were none from the AD cohort, and 2.6 and 6.8% from the MCI and cognitively normal cohorts, respectively. Our findings suggest that the Gen II immunoassays have potential utility in clinical routine to aid diagnosis of AD.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, beta-amyloid (1-42), biomarkers, cerebrospinal fluid, phosphorylated tau 181P, total tau
in
Clinical Chemistry and Laboratory Medicine
volume
61
issue
2
pages
234 - 244
publisher
De Gruyter
external identifiers
  • pmid:36282960
  • scopus:85141049860
ISSN
1434-6621
DOI
10.1515/cclm-2022-0516
language
English
LU publication?
yes
id
bd79e119-1b25-4e6d-a4da-227791b89bb1
date added to LUP
2022-12-21 14:52:01
date last changed
2025-12-14 03:02:29
@article{bd79e119-1b25-4e6d-a4da-227791b89bb1,
  abstract     = {{<p>Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys® CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine. Analytical performance was assessed using CSF samples measured with Elecsys CSF Gen II immunoassays on cobas e analyzers. Aβ42 Gen I/Gen II immunoassay method comparisons were performed (Passing-Bablok regression). Cut-off values were adjusted using estimated bias in biomarker levels between BioFINDER protocol aliquots/Gen I immunoassays and Gen II protocol aliquots/immunoassays. Distribution of Gen II immunoassay values was evaluated in AD, mild cognitive impairment (MCI), and cognitively normal cohorts; percentage observations outside the measuring range were derived. The Gen II immunoassays demonstrated good analytical performance, including repeatability, intermediate precision, lot-to-lot agreement (Pearson's r: ≥0.999), and platform agreement (Pearson's r: ≥0.995). Aβ42 Gen I/Gen II immunoassay measurements were strongly correlated (Pearson's r: 0.985-0.999). Aβ42 Gen II immunoassay cut-offs were adjusted to 1,030 and 800 ng/L, and pTau181/Aβ42 ratio cut-offs to 0.023 and 0.029, for Gen II and I protocols, respectively. No observations were below the lower limit of the measuring range; above the upper limit, there were none from the AD cohort, and 2.6 and 6.8% from the MCI and cognitively normal cohorts, respectively. Our findings suggest that the Gen II immunoassays have potential utility in clinical routine to aid diagnosis of AD.</p>}},
  author       = {{Blennow, Kaj and Stomrud, Erik and Zetterberg, Henrik and Borlinghaus, Niels and Corradini, Veronika and Manuilova, Ekaterina and Müller-Hübner, Laura and Quevenco, Frances Catherine and Rutz, Sandra and Hansson, Oskar}},
  issn         = {{1434-6621}},
  keywords     = {{Alzheimer's disease; beta-amyloid (1-42); biomarkers; cerebrospinal fluid; phosphorylated tau 181P; total tau}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{234--244}},
  publisher    = {{De Gruyter}},
  series       = {{Clinical Chemistry and Laboratory Medicine}},
  title        = {{Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1515/cclm-2022-0516}},
  doi          = {{10.1515/cclm-2022-0516}},
  volume       = {{61}},
  year         = {{2023}},
}