Derivation of cutoffs for the Elecsys® amyloid β (1–42) assay in Alzheimer's disease

Abstract Introduction An Elecsys® Amyloid β (Aβ [1–42]) immunoassay cutoff for classification of patients with Alzheimer's disease was investigated. Methods Cerebrospinal fluid samples collected from patients with mild-to-moderate Alzheimer's disease were analyzed by Elecsys® immunoassays: (1) Aβ (1–42), (2) total tau, and (3) phosphorylated tau. Cutoffs (Aβ [1–42] and ratios with tau) were estimated by method comparison between AlzBio3 ( n  = 206), mixture modeling ( n  = 216), and concordance with florbetapir F 18 imaging-based classification ( n  = 75). Results A 1065-pg/mL (95% confidence interval: 985–1153) Elecsys® Aβ (1–42) cutoff provided 94% overall percentage agreement with AlzBio3. Comparable cutoff estimates (95% confidence interval) were derived from mixture modeling (equally weighted: 1017 [949–1205] pg/mL; prevalence weighted: 1172 [1081–1344] pg/mL) and concordance with florbetapir F 18 imaging (visual read: 1198 [998–1591] pg/mL; automated: 1198 [1051–1638] pg/mL). Discussion Based on three approaches, a 1100-pg/mL Elecsys® Aβ (1–42) cutoff is suitable for clinical trials with similar populations and preanalytical handling.