Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Article type: Research Article

Authors: Sattlecker, Martina^{a; b; *} | Khondoker, Mizanur^{a; b} | Proitsi, Petroula^{a; b} | Williams, Stephen^c | Soininen, Hilkka^d | Kłoszewska, Iwona^e | Mecocci, Patrizia^f | Tsolaki, Magda^g | Vellas, Bruno^h | Lovestone, Simon^{a; b} | on behalf of the AddNeuroMed Consortium | Dobson, Richard JB^{a; b; *}

Affiliations: [a] Kings College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK | [b] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK | [c] SomaLogic, Boulder, Colorado, USA | [d] Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland | [e] Medical University of Lodz, Lodz, Poland | [f] Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy | [g] 3rd Department of Neurology, Aristotle University, Thessaloniki, Greece | [h] INSERM U 558, University of Toulouse, Toulouse, France

Correspondence: [*] Correspondence to: Martina Sattlecker and Richard Dobson, NIHR Biomedical Research Centre for Mental Health South London and Maudsley NHS Foundation Trust & King’s College London, Institute of Psychiatry & Neuroscience, De Crespigny Park, London, UK. Tel.: +44 (0)20 7848 0236; E-mails: [email protected], [email protected].

Abstract: Biomarkers of Alzheimer’s disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction in Mini Mental State Examination (MMSE) scores. Additionally, we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. We also found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects.

Keywords: Alzheimer’s disease, cognitive decline, complement cascade, cytokine-cytokine receptor interaction, plasma proteins

DOI: 10.3233/JAD-140669

Journal: Journal of Alzheimer's Disease, vol. 49, no. 4, pp. 1105-1114, 2016