title: Performance characteristics of plasma amyloid-beta 40 and 42 assays.
abstract: Identifying biomarkers of Alzheimer's disease (AD) risk will be critical to effective AD prevention. Levels of circulating amyloid-beta (Abeta) 40 and 42 may be candidate biomarkers. However, properties of plasma Abeta assays must be established. Using five different protocols, blinded samples were used to assess: intra-assay reproducibility; impact of EDTA vs. heparin anticoagulant tubes; and effect of time-to-blood processing. In addition, percent recovery of known Abeta concentrations in spiked samples was assessed. Median intra-assay coefficients of variation for the assay protocols ranged from 6-24% for Abeta(40), and 8-14% for Abeta(42). There were no systematic differences in reproducibility by collection method. Plasma concentrations of Abeta (particularly Abeta(42) appeared stable in whole blood kept in ice packs and processed as long as 24 hours after collection. Recovery of expected concentrations was modest, ranging from -24% to 44% recovery of Abeta(40), and 17% to 61% of Abeta(42). In conclusion, across five protocols, plasma Abeta(40) and Abeta(42) levels were measured with generally low error, and measurements appeared similar in blood collected in EDTA versus heparin. While these preliminary findings suggest that measuring plasma Abeta(40) and Abeta(42) may be feasible in varied research settings, additional work in this area is necessary.
authors.affiliation: Division of Aging, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ookereke@partners.org
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Okereke
authors.forename: Weiming
authors.initials: W
authors.lastname: Xia
authors.forename: Michael C
authors.initials: MC
authors.lastname: Irizarry
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.forename: Wei Q
authors.initials: WQ
authors.lastname: Qiu
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Pankaj D
authors.initials: PD
authors.lastname: Mehta
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Francine
authors.initials: F
authors.lastname: Grodstein
mesh_terms: D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000187:drug effects; D000925:Anticoagulants / Q000494:pharmacology; D015415:Biomarkers; D004492:Edetic Acid / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000097:blood* / Q000187:drug effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000925:Anticoagulants; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D006493:Heparin; D004492:Edetic Acid