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

• Published in: Alzheimer's & dementia : diagnosis, assessment & disease monitoring Vol. 10; no. 1; pp. 698 - 705
• Main Authors: Shaw, Leslie M., Waligorska, Teresa, Fields, Leona, Korecka, Magdalena, Figurski, Michal, Trojanowski, John Q., Eichenlaub, Udo, Wahl, Simone, Quan, Marian, Pontecorvo, Michael J., Lachno, D. Richard, Talbot, Jayne A., Andersen, Scott W., Siemers, Eric R., Dean, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2018; Elsevier; Wiley
• Subjects: Alzheimer's disease; Amyloid β; Biomarkers; Cerebrospinal fluid; CSF Biomarkers; Cutoff determination; Florbetapir F 18 imaging; Immunoassay; Method comparison; Patient selection; Immunoassay; Amyloid β; Biomarkers; Method comparison; Cutoff determination; Cerebrospinal fluid; Alzheimer's disease; Patient selection; Florbetapir F 18 imaging
• ISSN: 2352-8729; 2352-8729
• DOI: 10.1016/j.dadm.2018.07.002

An Elecsys® Amyloid β (Aβ [1–42]) immunoassay cutoff for classification of patients with Alzheimer's disease was investigated. 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). 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). Based on three approaches, a 1100-pg/mL Elecsys® Aβ (1–42) cutoff is suitable for clinical trials with similar populations and preanalytical handling. •Biomarkers can facilitate appropriate patient recruitment into clinical trials.•Amyloid beta measurement can aid the identification of amyloid-positive patients.•Similar cutoff estimates were derived by three different approaches.