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

INSIGHT-preAD Study Group, Alzheimer Precision Medicine Initiative (APMI)

Research output: Contribution to journalArticle

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)764-775
Number of pages12
JournalAlzheimer's and Dementia
Issue number6
StatePublished - 1 Jun 2019



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

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