Performance Characteristics of Plasma Amyloid-β 40 and 42 Assays

Article type: Research Article

Authors: Okereke, Olivia I.^{a; b; *} | Xia, Weiming^c | Irizarry, Michael C.^{d; 1} | Sun, Xiaoyan^e | Qiu, Wei Q.^e | Fagan, Anne M.^f | Mehta, Pankaj D.^g | Hyman, Bradley T.^d | Selkoe, Dennis J.^c | Grodstein, Francine^{a; b; h}

Affiliations: [a] Division of Aging, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA | [b] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA | [c] Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA | [d] Alzheimer Disease Research Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA | [e] Department of Psychiatry, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA, USA | [f] Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA | [g] Department of Immunology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA | [h] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

Correspondence: [*] Corresponding author: Dr. Olivia Okereke, Channing Laboratory 3rd floor, 181 Longwood Avenue, Boston, MA 02115, USA. Tel.: +1 617 525 2027; Fax: +1 617 525 2008; E-mail: ookereke@partners.org.

Note: [1] Dr. Irizarry's new affiliation is GlaxoSmithKline, Research Triangle Park, NC, USA.

Abstract: Identifying biomarkers of Alzheimer's disease (AD) risk will be critical to effective AD prevention. Levels of circulating amyloid-β (Aβ) 40 and 42 may be candidate biomarkers. However, properties of plasma Aβ 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 Aβ concentrations in spiked samples was assessed. Median intra-assay coefficients of variation for the assay protocols ranged from 6–24% for Aβ40, and 8–14% for Aβ42. There were no systematic differences in reproducibility by collection method. Plasma concentrations of Aβ (particularly Aβ42) 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 Aβ40, and 17% to 61% of Aβ42. In conclusion, across five protocols, plasma Aβ40 and Aβ42 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 Aβ40 and Aβ42 may be feasible in varied research settings, additional work in this area is necessary.

Keywords: Alzheimer's disease, amyloid, assay reliability, biomarker, quality control

DOI: 10.3233/JAD-2009-0948

Journal: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 277-285, 2009