Rabe, Christina;
Bittner, Tobias;
Jethwa, Alexander;
Suridjan, Ivonne;
Manuilova, Ekaterina;
Friesenhahn, Michel;
Stomrud, Erik;
... Alzheimer's Disease Neuroimaging Initiative† and the Swedish Bio; + view all
(2022)
Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
10.1002/alz.12801.
(In press).
Preview |
PDF
Clinical performance and robustness evaluation.pdf - Published Version Download (1MB) | Preview |
Abstract
INTRODUCTION: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ42 /Aβ40 for amyloid positivity prescreening. METHODS: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma Aβ42 /Aβ40 evaluated the actionability of plasma Aβ42 /Aβ40 , and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. RESULTS: Elecsys plasma Aβ42 /Aβ40 could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in Aβ42 and/or Aβ40 cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. DISCUSSION: Implementing plasma Aβ42 /Aβ40 for routine clinical use may pose significant challenges, with misclassification risks. HIGHLIGHTS: Plasma Aβ42 /Aβ40 ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma Aβ42 /Aβ40 had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.
| Type: | Article |
|---|---|
| Title: | Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12801 |
| Publisher version: | https://doi.org/10.1002/alz.12801 |
| Language: | English |
| Additional information: | © 2022 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Alzheimer's disease, amyloid, biomarkers, blood biomarkers, prescreening |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10156767 |
Archive Staff Only
 |
View Item |
