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

Abstract 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 Aβ 1–40 /Aβ 1–42 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 Aβ 1–40 /Aβ 1–42 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 Aβ 1–40 /Aβ 1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.