Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

Alzheimers Dement. 2019 Jun;15(6):764-775. doi: 10.1016/j.jalz.2019.03.009. Epub 2019 May 18.


Introduction: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management.

Methods: We investigated whether plasma concentrations of the Aβ1-40/Aβ1-42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning.

Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma Aβ1-40/Aβ1-42 ratio. The accuracy is not affected by the apolipoprotein E (APOE) ε4 allele, sex, or age.

Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1-40/Aβ1-42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.

Keywords: Alzheimer's disease; Amyloid PET; Classification and regression trees (CART); Machine learning; Plasma amyloid β; Simoa immunoassay; Subjective memory complainers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Amyloid beta-Peptides
  • Biomarkers / blood*
  • Brain / metabolism
  • Cerebral Amyloid Angiopathy / diagnosis*
  • Cognition / physiology*
  • Cohort Studies
  • Female
  • Humans
  • Machine Learning
  • Male
  • Memory / physiology
  • Peptide Fragments
  • Positron-Emission Tomography


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)

Supplementary concepts

  • Amyloid angiopathy