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2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

Leuzy, A. LU ; Ashton, N. J. ; Mattsson-Carlgren, N. LU orcid ; Dodich, A. ; Boccardi, M. ; Corre, J. ; Drzezga, A. ; Nordberg, A. ; Ossenkoppele, R. LU and Zetterberg, H. LU , et al. (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2121-2139
Abstract

Purpose: In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 amino-acid isoform of amyloid-β (Aβ42), phosphorylated-tau (P-tau), and Total-tau (T-tau)—with the aim to accelerate their development and clinical implementation. The aim of this work is to update the current validation status of CSF AD biomarkers based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva.... (More)

Purpose: In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 amino-acid isoform of amyloid-β (Aβ42), phosphorylated-tau (P-tau), and Total-tau (T-tau)—with the aim to accelerate their development and clinical implementation. The aim of this work is to update the current validation status of CSF AD biomarkers based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of CSF AD biomarkers was assessed based on the Biomarker Roadmap methodology before the meeting and presented and discussed during the workshop. Results: By comparison to the previous 2017 Geneva Roadmap meeting, the primary advances in CSF AD biomarkers have been in the area of a unified protocol for CSF sampling, handling and storage, the introduction of certified reference methods and materials for Aβ42, and the introduction of fully automated assays. Additional advances have occurred in the form of defining thresholds for biomarker positivity and assessing the impact of covariates on their discriminatory ability. Conclusions: Though much has been achieved for phases one through three, much work remains in phases four (real world performance) and five (assessment of impact/cost). To a large degree, this will depend on the availability of disease-modifying treatments for AD, given these will make accurate and generally available diagnostic tools key to initiate therapy.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Aβ42, CSF, P-tau, strategic roadmap, T-tau
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
19 pages
publisher
Springer
external identifiers
  • scopus:85102189037
  • pmid:33674895
ISSN
1619-7070
DOI
10.1007/s00259-021-05258-7
language
English
LU publication?
yes
id
019f8817-6bc9-489f-8381-ddd0338a2f3a
date added to LUP
2021-03-19 08:52:02
date last changed
2024-06-13 09:02:54
@article{019f8817-6bc9-489f-8381-ddd0338a2f3a,
  abstract     = {{<p>Purpose: In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer’s disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers—encompassing the 42 amino-acid isoform of amyloid-β (Aβ42), phosphorylated-tau (P-tau), and Total-tau (T-tau)—with the aim to accelerate their development and clinical implementation. The aim of this work is to update the current validation status of CSF AD biomarkers based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of CSF AD biomarkers was assessed based on the Biomarker Roadmap methodology before the meeting and presented and discussed during the workshop. Results: By comparison to the previous 2017 Geneva Roadmap meeting, the primary advances in CSF AD biomarkers have been in the area of a unified protocol for CSF sampling, handling and storage, the introduction of certified reference methods and materials for Aβ42, and the introduction of fully automated assays. Additional advances have occurred in the form of defining thresholds for biomarker positivity and assessing the impact of covariates on their discriminatory ability. Conclusions: Though much has been achieved for phases one through three, much work remains in phases four (real world performance) and five (assessment of impact/cost). To a large degree, this will depend on the availability of disease-modifying treatments for AD, given these will make accurate and generally available diagnostic tools key to initiate therapy.</p>}},
  author       = {{Leuzy, A. and Ashton, N. J. and Mattsson-Carlgren, N. and Dodich, A. and Boccardi, M. and Corre, J. and Drzezga, A. and Nordberg, A. and Ossenkoppele, R. and Zetterberg, H. and Blennow, K. and Frisoni, G. B. and Garibotto, V. and Hansson, O.}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Aβ42; CSF; P-tau; strategic roadmap; T-tau}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2121--2139}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework}},
  url          = {{http://dx.doi.org/10.1007/s00259-021-05258-7}},
  doi          = {{10.1007/s00259-021-05258-7}},
  volume       = {{48}},
  year         = {{2021}},
}