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

Leslie M Shaw; Teresa Waligorska; Leona Fields; Magdalena Korecka; Michal Figurski; John Q Trojanowski; Udo Eichenlaub; Simone Wahl; Marian Quan; Michael J Pontecorvo; D Richard Lachno; Jayne A Talbot; Scott W Andersen; Eric R Siemers; Robert A Dean

doi:10.1016/j.dadm.2018.07.002

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

Alzheimers Dement (Amst). 2018 Aug 11:10:698-705. doi: 10.1016/j.dadm.2018.07.002. eCollection 2018.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Roche Diagnostics GmbH, Bavaria, Germany.
³ Roche Diagnostics, Indianapolis, IN, USA.
⁴ Clinical Development, Avid Radiopharmaceuticals, Philadelphia, PA, USA.
⁵ Eli Lilly and Company, Windlesham, Surrey, UK.
⁶ Eli Lilly and Company, Indianapolis, IN, USA.
⁷ Indiana University School of Medicine, Indianapolis, IN, USA.

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.

Keywords: Alzheimer's disease; Amyloid β; Biomarkers; Cerebrospinal fluid; Cutoff determination; Florbetapir F 18 imaging; Immunoassay; Method comparison; Patient selection.