Peripheral α-Defensins 1 and 2 are Elevated in Alzheimer's Disease

Article type: Research Article

Authors: Watt, Andrew D.^{a; c} | Perez, Keyla A.^{a; c} | Ang, Ching-Seng^d | O'Donnell, Paul^d | Rembach, Alan^a | Pertile, Kelly K.^a | Rumble, Rebecca L.^a | Trounson, Brett O.^a | Fowler, Christopher J.^a | Faux, Noel G.^a | Masters, Colin L.^a | Villemagne, Victor L.^{a; e} | Barnham, Kevin J.^{a; b; c; *}

Affiliations: [a] The Florey Institute of Neuroscience and Mental Health, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia | [b] Department of Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia | [c] The Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia | [d] Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, VIC, Australia | [e] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia

Correspondence: [*] Correspondence to: Kevin Barnham, The Florey Institute of Neuroscience and Mental Health and Department of Pharmacology, The University of Melbourne, VIC, 3010 Australia. Tel.: +61 3 83442555; Fax: +61 3 93476750; E-mail: [email protected].

Abstract: Biomarkers enabling the preclinical identification of Alzheimer's disease (AD) remain one of the major unmet challenges in the field. The blood cellular fractions offer a viable alternative to current cerebrospinal fluid and neuroimaging modalities. The current study aimed to replicate our earlier reports of altered binding within the AD-affected blood cellular fraction to copper-loaded immobilized metal affinity capture (IMAC) arrays. IMAC and anti-amyloid-β (Aβ) antibody arrays coupled with mass spectrometry were used to analyze blood samples collected from 218 participants from within the AIBL Study of Aging. Peripheral Aβ was fragile and prone to degradation in the AIBL samples, even when stored at −80°C. IMAC analysis of the AIBL samples lead to the isolation and identification of alpha-defensins 1 and 2 at elevated levels in the AD periphery, validating earlier findings. Alpha-defensins 1 and 2 were elevated in AD patients indicating that an inflammatory phenotype is present in the AD periphery; however, peripheral Aβ levels are required to supplement their prognostic power.

Keywords: α-defensins, Alzheimer's disease, amyloid-β, biomarkers, blood, inflammation, mass spectrometry

DOI: 10.3233/JAD-142286

Journal: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1131-1143, 2015