Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Article type: Research Article

Authors: Lui, James K.^{a; b;} | Laws, Simon M.^{a; b;} | Li, Qiao-Xin^{c; d} | Villemagne, Victor L.^{c; e} | Ames, David^{f; g} | Brown, Belinda^{a; b} | Bush, Ashley I.^{c; d} | De Ruyck, Karl^{a; b} | Dromey, Jasmin^a | Ellis, Kathryn A.^{c; f; g} | Faux, Noel G.^{c; h} | Foster, Jonathan^{a; b; i} | Fowler, Christopher^c | Gupta, Veer^{a; b} | Hudson, Peter^{c; j} | Laughton, Katrina^{c; d} | Masters, Colin L.^{c; h} | Pertile, Kelly^c | Rembach, Alan^c | Rimajova, Mira^{a; b} | Rodrigues, Mark^{a; b} | Rowe, Christopher C.^e | Rumble, Rebecca^c | Szoeke, Cassandra^{g; j} | Taddei, Kevin^{a; b} | Taddei, Tania^{a; b} | Trounson, Brett^c | Ward, Vanessa^{a; b} | Martins, Ralph N.^{a; b; *} | for the AIBL Research Group^k

Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia | [b] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia, Australia | [c] Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia | [d] Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia | [e] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia | [f] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, St. Vincent's Aged Psychiatry Service, St George's Hospital, Victoria Australia | [g] National Ageing Research Institute, Parkville, Victoria, Australia | [h] Centre for Neuroscience, The University of Melbourne, Parkville, Australia | [i] Neurosciences Unit, Health Department of Western Australia, Perth, Western Australia, Australia | [j] CSIRO, Parkville, Victoria, Australia | [k] http://www.aibl.csiro.au/

Correspondence: [*] Correspondence to: Professor Ralph N. Martins, School of Exercise, Biomedical and Health Science, Edith Cowan University, 270 Joondalup Dr, Joondalup, WA 6027, Australia. Tel.: +61 08 6304 5456; Fax: +61 08 6304 5851; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Aβ as an AD biomarker and its relationship with Aβ load and to determine the effect of different assay methods on the interpretation of Aβ levels. Plasma Aβ1-40, Aβ1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Aβ levels were compared to Aβ load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Aβ1-42 and Aβ1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Aβ load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Aβ isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Aβ has diagnostic value in a panel of biomarkers.

Keywords: Alzheimer's disease, amyloid-β, biomarkers, diagnosis, Pittsburgh Compound B, positron-emission topography

DOI: 10.3233/JAD-2010-090249

Journal: Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 1233-1242, 2010