Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening

Alzheimers Dement. 2023 Apr;19(4):1393-1402. doi: 10.1002/alz.12801. Epub 2022 Sep 23.


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.

Keywords: Alzheimer's disease; amyloid; biomarkers; blood biomarkers; prescreening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Amyloid / metabolism
  • Amyloid beta-Peptides
  • Amyloidosis*
  • Biomarkers
  • Brain / metabolism
  • Humans
  • Peptide Fragments


  • Amyloid beta-Peptides
  • Biomarkers
  • Amyloid
  • Peptide Fragments