Selenium Levels in Serum, Red Blood Cells, and Cerebrospinal Fluid of Alzheimer’s Disease Patients: A Report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL)

Article type: Research Article

Authors: Cardoso, Bárbara R.^{a; b; *} | Hare, Dominic J.^{a; c} | Bush, Ashley I.^{a; d} | Li, Qiao-Xin^a | Fowler, Christopher J.^a | Masters, Colin L.^a | Martins, Ralph N.^e | Ganio, Katherine^a | Lothian, Amber^{a; d} | Mukherjee, Soumya^{a; f} | Kapp, Eugene A.^{a; d; g} | Roberts, Blaine R.^{a; d; *} | The AIBL research group^h

Affiliations: [a] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia | [b] Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, SP, Brazil | [c] Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, NSW, Australia | [d] Cooperative Research Centre for Mental Health, Parkville, VIC, Australia | [e] Edith Cowan University, School of Exercise, Biomedical and Health Sciences, Joondalup, WA, Australia | [f] Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata, India | [g] Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia | [h] http://www.aibl.csiro.au

Correspondence: [*] Correspondence to: Bárbara R. Cardoso and Blaine R. Roberts, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia. Tel.: +61 450 633 537; E-mails: [email protected]; [email protected] (B.R. Cardoso); [email protected] (B.R. Roberts).

Abstract: Selenium (Se) protects cells against oxidative stress damage through a range of bioactive selenoproteins. Increased oxidative stress is a prominent feature of Alzheimer’s disease (AD), and previous studies have shown that Se deficiency is associated with age-related cognitive decline. In this study, we assessed Se status in different biofluids from a subgroup of participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. As Se in humans can either be an active component of selenoproteins or inactive via non-specific incorporation into other proteins, we used both size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and tandem mass spectrometry to characterize selenoproteins in serum. We observed no differences in total Se concentration in serum or cerebrospinal fluid of AD subjects compared to mildly cognitively impairment patients and healthy controls. However, Se levels in erythrocytes were decreased in AD compared to controls. SEC-ICP-MS analysis revealed a dominant Se-containing fraction. This fraction was subjected to standard protein purification and a bottom-up proteomics approach to confirm that the abundant Se in the fraction was due, in part, to selenoprotein P. The lack of change in the Se level is at odds with our previous observations in a Brazilian population deficient in Se, and we attribute this to the Australian cohort being Se-replete.

Keywords: Alzheimer’s disease, cognition, selenium, selenocysteine, selenoproteins

DOI: 10.3233/JAD-160622

Journal: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 183-193, 2017