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. 2021;83(3):1161-1171.
doi: 10.3233/JAD-200871.

Plasma Sphingomyelins in Late-Onset Alzheimer's Disease

Gianna Fote  1 , Jie Wu  1   2 , Mark Mapstone  3 , Fabio Macciardi  4 , Massimo S Fiandaca  5   6   7 , Howard J Federoff  3
Affiliations

Plasma Sphingomyelins in Late-Onset Alzheimer's Disease

Gianna Fote et al. J Alzheimers Dis. 2021.

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.

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Figures

Fig. 1.
Fig. 1.
Sphingomyelin levels do not significantly differ cognitive state or age. A) Total plasma SM levels in μMol/L separated by disease state. B) Total plasma SM levels in μMol/L separated by gender and disease state. Box plot center line represents mean, upper and lower bounds are 25th and 75th percentile. Whiskers generated by Tukey method; outliers plotted as points beyond whiskers. C) Scatter plots of plasma levels of the sum of all SM species μMol/L by age in all subjects. Each point represents one individual. Linear regression and 95% confidence intervals shown. D) Scatter plots of plasma levels of the sum of all SM species μMol/L by age in males. E) Scatter plots of plasma levels of the sum of all SM species μMol/L by age in females.
Fig. 2.
Fig. 2.
Plasma levels of SM (OH) C14:1 in μMol/L. Box plot center line represents mean, upper and lower bounds are 25th and 75th percentile. Whiskers generated by Tukey method; outliers plotted as points beyond whiskers. ANCOVA analysis revealed p < 0.05 (A) and p = 0.055 (B). Asterisk indicates significant differences in pairwise comparisons after adjustment for age and gender, p < 0.05.
See this image and copyright information in PMC

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