Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease
(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
- Blennow, Kaj LU ; Stomrud, Erik LU ; Zetterberg, Henrik LU ; Borlinghaus, Niels ; Corradini, Veronika ; Manuilova, Ekaterina ; Müller-Hübner, Laura ; Quevenco, Frances Catherine ; Rutz, Sandra and Hansson, Oskar LU
- organization
- publishing date
- 2023
- 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
- 2024-09-20 09:13:55
@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}}, }