Exploration of Plasma Lipids in Mild Cognitive Impairment due to Alzheimer’s Disease

Article type: Research Article

Authors: Bergland, Anne Katrine^{a; b; 1; *} | Proitsi, Petroula^{c; 1} | Kirsebom, Bjørn-Eivind^{d; e} | Soennesyn, Hogne^a | Hye, Abdul^c | Larsen, Alf Inge^{b; f} | Xu, Jin^{c; g} | Legido-Quigley, Cristina^{g; h} | Rajendran, Lawrenceⁱ | Fladby, Tormod^{j; k} | Aarsland, Dag^{a; i}

Affiliations: [a] Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway | [b] Department of Clinical Science, University of Bergen, Bergen, Norway | [c] Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK | [d] Department of Neurology, University Hospital of North Norway, Tromsø, Norway | [e] Department of Psychology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway | [f] Department of Cardiology, Stavanger University Hospital, Stavanger, Norway | [g] Institute of Pharmaceutical Science, King’s College London, London, UK | [h] Systems Medicine, Steno Diabetes Centre, Copenhagen, Denmark | [i] UK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK | [j] Department of Neurology, Akershus University Hospital, Lørenskog, Norway | [k] Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway

Correspondence: [*] Correspondence to: Anne Katrine Bergland, Stavanger University Hospital, Department of Internal Medicine, Postboks 8100, 4068 Stavanger, Norway. Tel.: +47 91595103; Fax: +47 51515161; E-mail: [email protected].

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

Abstract: Background:Lipids have important structural roles in cell membranes and changes to these membrane lipids may influence β- and γ-secretase activities and thus contribute to Alzheimer’s disease (AD) pathology. Objective:To explore baseline plasma lipid profiling in participants with mild cognitive impairment (MCI) with and without AD pathology. Methods:We identified 261 plasma lipids using reversed-phase liquid chromatography/mass spectrometry in cerebrospinal fluid amyloid positive (Aβ+) or negative (Aβ–) participants with MCI as compared to controls. Additionally, we analyzed the potential associations of plasma lipid profiles with performance on neuropsychological tests at baseline and after two years. Results:Sphingomyelin (SM) concentrations, particularly, SM(d43:2), were lower in MCI Aβ+ individuals compared to controls. Further, SM(d43:2) was also nominally reduced in MCI Aβ+ individuals compared to MCI Aβ–. No plasma lipids were associated with performance on primary neuropsychological tests at baseline or between the two time points after correction for multiple testing. Conclusion:Reduced plasma concentrations of SM were associated with AD.

Keywords: Alzheimer’s disease, lipid, mild cognitive impairment, sphingomyelin

DOI: 10.3233/JAD-200441

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1117-1127, 2020