Clinical performance and robustness evaluation of plasma amyloid‐β42/40 prescreening. Issue 4 (23rd September 2022)

• Record Type: Journal Article
• Authors: Rabe, Christina; Bittner, Tobias; Jethwa, Alexander; Suridjan, Ivonne; Manuilova, Ekaterina; Friesenhahn, Michel; Stomrud, Erik; Zetterberg, Henrik; Blennow, Kaj; Hansson, Oskar
• Is Part Of: Alzheimer's & dementia. Volume 19:Issue 4(2023)
• Page Start: 1393
• Page End: 1402
• Publication Date: 2022-09-23
• Subjects: Alzheimer's disease -- amyloid -- biomarkers -- blood biomarkers -- prescreening; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12801
• Languages: English
• ISSNs: 1552-5260

Abstract

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.