TY  - JOUR
AU  - Ashton, N. J.
AU  - Leuzy, A.
AU  - Karikari, T. K.
AU  - Mattsson-Carlgren, N.
AU  - Dodich, A.
AU  - Boccardi, M.
AU  - Corre, J.
AU  - Drzezga, Alexander
AU  - Nordberg, A.
AU  - Ossenkoppele, R.
AU  - Zetterberg, H.
AU  - Blennow, K.
AU  - Frisoni, Giovanni B
AU  - Garibotto, V.
AU  - Hansson, O.
TI  - The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.
JO  - European journal of nuclear medicine and molecular imaging
VL  - 48
IS  - 7
SN  - 1619-7089
CY  - Heidelberg [u.a.]
PB  - Springer-Verl.
M1  - DZNE-2021-00636
SP  - 2140 - 2156
PY  - 2021
AB  - 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.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.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.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.
KW  - Alzheimer Disease: diagnostic imaging
KW  - Amyloid beta-Peptides
KW  - Biomarkers
KW  - Humans
KW  - Peptide Fragments
KW  - Tomography, X-Ray Computed
KW  - tau Proteins
KW  - Alzheimer’s disease (Other)
KW  - Aβ40 (Other)
KW  - Aβ42 (Other)
KW  - Blood (Other)
KW  - P-tau (Other)
KW  - Strategic roadmap (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33677733
C2  - pmc:PMC8175325
DO  - DOI:10.1007/s00259-021-05253-y
UR  - https://pub.dzne.de/record/155430
ER  -