Cited by 147Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsClinical Laboratory Practices and Quality Control

Concordance between different amyloid immunoassays and visual amyloid positron emission tomographic assessment.

Open access
Janelidze, Shorena, Pannee, Josef, Mikulskis, Alvydas, Chiao, Ping, Zetterberg, Henrik, Blennow, Kaj, Hansson, Oskar·2017·JAMA Neurology

Abstract

Importance: Visual assessment of amyloid positron emission tomographic (PET) images has been approved by regulatory authorities for clinical use. Several immunoassays have been developed to measure β-amyloid (Aβ) 42 in cerebrospinal fluid (CSF). The agreement between CSF Aβ42 measures from different immunoassays and visual PET readings may influence the use of CSF biomarkers and/or amyloid PET assessment in clinical practice and trials. Objective: To determine the concordance between CSF Aβ42 levels measured using 5 different immunoassays and visual amyloid PET analysis. Design, Setting, and Participants: The study included 262 patients with mild cognitive impairment or subjective cognitive decline from the Swedish BioFINDER (Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably) cohort (recruited from September 1, 2010, through December 31, 2014) who had undergone flutemetamol F 18 ([18F]flutemetamol)-labeled PET. Levels of CSF Aβ42 were analyzed using the classic INNOTEST and the newer modified INNOTEST, fully automated Lumipulse (FL), EUROIMMUN (EI), and Meso Scale Discovery (MSD) assays. Concentrations of CSF Aβ were assessed using an antibody-independent mass spectrometry-based reference measurement procedure. Main Outcomes and Measures: The concordance of CSF Aβ42 levels and Aβ42:Aβ40 and Aβ42:tau ratios with visual [18F]flutemetamol PET status. Results: Of 262 participants (mean [SD] age, 70.9 [5.5] years), 108 were women (41.2%) and 154 were men (58.8%). The mass spectrometry-derived Aβ42 values showed higher correlations with the modified Aβ42-INNOTEST (r = 0.97), Aβ42-FL (r = 0.93), Aβ42-EI (r = 0.93), and Aβ42-MSD (r = 0.95) assays compared with the classic Aβ42-INNOTEST assay (r = 0.88; P ≤ .01). The signal in the classic Aβ42-INNOTEST assay was partly quenched by recombinant Aβ1-40 peptide. However, the classic Aβ42-INNOTEST assay showed better concordance with visual [18F]flutemetamol PET status (area under the receiver operating characteristic curve [AUC], 0.92) compared with the newer assays (AUCs, 0.87-0.89; P ≤ .01). The accuracies of the newer assays improved significantly when Aβ42:Aβ40 (AUCs, 0.93-0.95; P ≤ .01), Aβ42 to total tau (T-tau) (AUCs, 0.94; P ≤ .05), or Aβ42 to phosphorylated tau (P-tau) (AUCs, 0.94-0.95; P ≤ .001) ratios were used. A combination of the Aβ42:Aβ40 ratio and T-tau or P-tau level did not improve the accuracy compared with the ratio alone. Conclusions and Relevance: Concentrations of CSF Aβ42 derived from the new immunoassays (modified INNOTEST, FL, EI, and MSD) may correlate better with the antibody-independent mass spectrometry-based reference measurement procedure and may show improved agreement with visual [18F]flutemetamol PET assessment when using the Aβ42:Aβ40 or Aβ42:tau ratios. These findings suggest the benefit of implementing the CSF Aβ42:Aβ40 or Aβ42:tau ratios as a biomarker of amyloid deposition in clinical practice and trials.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jamaneurol.2017.2814

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 36 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Janelidze S, Zetterberg H, Mattsson N, et al; Swedish BioFINDER study group. CSF Aβ42:Aβ40 and Aβ42:Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016;3 (3):154-165.

Cited by

Sorted by citations

Authors
Janelidze, S., Pannee, J., Mikulskis, A., Chiao, P., Zetterberg, H., Blennow, K., & Hansson, O.
Affiliations
  • Lund University (SE)
  • University of Gothenburg (SE)
  • Biogen (United States) (US)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Janelidze, Shorena
Venue
JAMA Neurology
Published
2017-12-01
Volume
74
Issue
12
Pages
1492
ISSN
2168-6149 (ISSN-L)
OpenAlex
W2767595531
Cited by
147
References
36
Citations by year
2026: 9 · 2025: 13 · 2024: 19 · 2023: 13 · 2022: 19 · 2021: 24 · 2020: 23 · 2019: 15 · 2018: 12
FWCI
11.24
Type
journal article
Language
en
Open access
Locations
  • JAMA Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Australian Government
  • Vetenskapsrådet
  • Fujirebio Europe
  • Marcus och Amalia Wallenbergs minnesfond
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
amyloid PET, amyloid-beta 42, cerebrospinal fluid biomarkers, 18F-flutemetamol, Meso Scale Discovery, Aβ42/Aβ40 ratio, mild cognitive impairment
MeSH terms
Aged, Amyloid, Aniline Compounds, Cerebral Cortex, Female, Humans, Immunoassay, Male, Peptide Fragments, ROC Curve, Sweden, Cohort Studies, Amyloid beta-Peptides, tau Proteins, Radiopharmaceuticals, Area Under Curve, Positron-Emission Tomography, Benzothiazoles, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review