Plasma Sphingomyelins in Late-Onset Alzheimer’s Disease

Article type: Research Article

Authors: Fote, Gianna^{a; *} | Wu, Jie^{a; b} | Mapstone, Mark^c | Macciardi, Fabio^d | Fiandaca, Massimo S.^{e; f; g} | Federoff, Howard J.^{c; *}

Affiliations: [a] Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA | [b] Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA | [c] Department of Neurology, University of California, Irvine, Irvine, CA, USA | [d] Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA | [e] Translational Laboratory and Biorepository, Department of Neurology, University of California Irvine School of Medicine, Irvine, CA, USA | [f] Department of Neurological Surgery, University of California Irvine School of Medicine, Irvine, CA, USA | [g] Department of Anatomy & Neurobiology, University of California Irvine School of Medicine, Irvine, CA, USA

Correspondence: [*] Correspondence to: Gianna M. Fote, UC Irvine School of Medicine, 385 S. Manchester Ave, Unit 2096, Orange, CA 92686, USA. Tel.: +1 310 924 4415; E-mail: [email protected]; Howard Federoff, MD, PhD, Distinguished Professor, Neurology, UC Irvine School of Medicine, Orange, CA 92686, USA. Tel.: +1 240 281 2598; E-mail: [email protected].

Abstract: Background:Altered plasma levels of sphingolipids, including sphingomyelins (SM), have been found in mouse models of Alzheimer’s disease (AD) and in AD patient plasma samples. Objective:This study assesses fourteen plasma SM species in a late-onset AD (LOAD) patient cohort (n = 138). Methods:Specimens from control, preclinical, and symptomatic subjects were analyzed using targeted mass-spectrometry-based metabolomic methods. Results:Total plasma SM levels were not significantly affected by age or cognitive status. However, one metabolite that has been elevated in manifest AD in several recent studies, SM OHC14:1, was reduced significantly in pre-clinical AD and MCI relative to normal controls. Conclusion:We recommend additional comprehensive plasma lipidomics in experimental and clinical biospecimens related to LOAD that might advance the utility of plasma sphingomyelin levels in molecular phenotyping and interpretations of pathobiological mechanisms.

Keywords: Alzheimer’s disease, metabolomics, plasma, sphingolipids, sphingomyelin

DOI: 10.3233/JAD-200871

Journal: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1161-1171, 2021