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CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression : A study of fully automated immunoassays in BioFINDER and ADNI cohorts

Hansson, Oskar LU orcid ; Seibyl, John ; Stomrud, Erik LU orcid ; Zetterberg, Henrik LU ; Trojanowski, John Q. ; Bittner, Tobias ; Lifke, Valeria ; Corradini, Veronika ; Eichenlaub, Udo and Batrla, Richard , et al. (2018) In Alzheimer's and Dementia 14(11). p.1470-1481
Abstract

Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid-β1–42 (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with... (More)

Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid-β1–42 (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.

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type
Contribution to journal
publication status
published
subject
keywords
Amyloid PET concordance, Amyloid-β (1–42), Biomarker validation, Clinical progression, CSF biomarkers, Cutoffs, Phosphorylated tau (pTau), Total tau (tTau)
in
Alzheimer's and Dementia
volume
14
issue
11
pages
1470 - 1481
publisher
Wiley
external identifiers
  • pmid:29499171
  • scopus:85044290649
ISSN
1552-5260
DOI
10.1016/j.jalz.2018.01.010
language
English
LU publication?
yes
id
9d721213-1523-4d6d-b249-6fa9025688b8
date added to LUP
2018-04-09 14:28:29
date last changed
2024-04-15 06:01:09
@article{9d721213-1523-4d6d-b249-6fa9025688b8,
  abstract     = {{<p>Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid-β<sub>1–42</sub> (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [<sup>18</sup>F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [<sup>18</sup>F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.</p>}},
  author       = {{Hansson, Oskar and Seibyl, John and Stomrud, Erik and Zetterberg, Henrik and Trojanowski, John Q. and Bittner, Tobias and Lifke, Valeria and Corradini, Veronika and Eichenlaub, Udo and Batrla, Richard and Buck, Katharina and Zink, Katharina and Rabe, Christina and Blennow, Kaj and Shaw, Leslie M.}},
  issn         = {{1552-5260}},
  keywords     = {{Amyloid PET concordance; Amyloid-β (1–42); Biomarker validation; Clinical progression; CSF biomarkers; Cutoffs; Phosphorylated tau (pTau); Total tau (tTau)}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1470--1481}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression : A study of fully automated immunoassays in BioFINDER and ADNI cohorts}},
  url          = {{http://dx.doi.org/10.1016/j.jalz.2018.01.010}},
  doi          = {{10.1016/j.jalz.2018.01.010}},
  volume       = {{14}},
  year         = {{2018}},
}