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The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers

Ashton, N. J. ; Leuzy, A. LU ; Karikari, T. K. ; Mattsson-Carlgren, N. LU orcid ; Dodich, A. ; Boccardi, M. ; Corre, J. ; Drzezga, A. ; Nordberg, A. and Ossenkoppele, R. LU , et al. (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2140-2156
Abstract

Purpose: The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. Methods: A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography... (More)

Purpose: The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. Methods: A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Results: Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Conclusions: Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 – with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Aβ40, Aβ42, Blood, P-tau, Strategic roadmap
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
17 pages
publisher
Springer
external identifiers
  • pmid:33677733
  • scopus:85102275733
ISSN
1619-7070
DOI
10.1007/s00259-021-05253-y
language
English
LU publication?
yes
id
048db6ca-4233-4009-8afa-cdaabac97887
date added to LUP
2021-03-29 10:50:39
date last changed
2024-06-16 11:18:02
@article{048db6ca-4233-4009-8afa-cdaabac97887,
  abstract     = {{<p>Purpose: The development of blood biomarkers that reflect Alzheimer’s disease (AD) pathophysiology (phosphorylated tau and amyloid-β) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. Methods: A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Results: Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aβ remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aβ, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Conclusions: Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 – with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.</p>}},
  author       = {{Ashton, N. J. and Leuzy, A. and Karikari, T. K. 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; Aβ40; Aβ42; Blood; P-tau; Strategic roadmap}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2140--2156}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers}},
  url          = {{http://dx.doi.org/10.1007/s00259-021-05253-y}},
  doi          = {{10.1007/s00259-021-05253-y}},
  volume       = {{48}},
  year         = {{2021}},
}