en
Scientific article
Review
Open access
English

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

Published inEuropean journal of nuclear medicine and molecular imaging, vol. 48, no. 7, p. 2140-2156
Publication date2021-07
First online date2021-03-06
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 (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.

eng
Keywords
  • Alzheimer’s disease
  • Aβ40
  • Aβ42
  • Blood
  • P-tau
  • Strategic roadmap
  • Alzheimer Disease / diagnostic imaging
  • Amyloid beta-Peptides
  • Biomarkers
  • Humans
  • Peptide Fragments
  • Tomography, X-Ray Computed
  • Tau Proteins
Citation (ISO format)
ASHTON, N J et al. The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers. In: European journal of nuclear medicine and molecular imaging, 2021, vol. 48, n° 7, p. 2140–2156. doi: 10.1007/s00259-021-05253-y
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1619-7070
116views
43downloads

Technical informations

Creation20/01/2022 07:55:00
First validation20/01/2022 07:55:00
Update time16/03/2023 06:33:14
Status update16/03/2023 06:33:13
Last indexation12/02/2024 12:22:47
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack