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Published on: October 24, 2017
Plasma Sphingomyelins in Late-Onset Alzheimer's Disease
Gianna Fote1, Jie Wu1,2, Mark Mapstone3
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
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.
Insights
Plasma sphingomyelin levels may indicate early Alzheimer's disease (AD). A specific sphingomyelin (SM OHC14:1) was reduced in preclinical AD and mild cognitive impairment (MCI), suggesting potential as an early biomarker for late-onset AD (LOAD).
Area of Science:
- Neuroscience
- Metabolomics
- Biochemistry
Background:
- Altered plasma sphingolipids, including sphingomyelins (SM), are observed in Alzheimer's disease (AD) models and patients.
- Previous research indicates potential roles for sphingolipids in AD pathogenesis.
Purpose of the Study:
- To investigate plasma sphingomyelin (SM) species in a cohort of late-onset Alzheimer's disease (LOAD) patients.
- To identify specific SM metabolites associated with different stages of cognitive decline.
Main Methods:
- Targeted mass-spectrometry-based metabolomic analysis of plasma samples.
- Analysis of fourteen plasma SM species in 138 individuals across control, preclinical AD, and symptomatic AD groups.
- Assessment of SM levels in relation to age and cognitive status.
Main Results:
- Total plasma SM levels did not significantly differ with age or cognitive status.
- SM OHC14:1, a metabolite previously elevated in manifest AD, was significantly reduced in preclinical AD and mild cognitive impairment (MCI) compared to controls.
- This finding suggests SM OHC14:1 may be a sensitive indicator of early AD-related changes.
Conclusions:
- Plasma sphingomyelin profiles, particularly SM OHC14:1, show promise for early molecular phenotyping in LOAD.
- Further comprehensive plasma lipidomics studies are recommended to validate these findings and explore their pathobiological implications.
- SM levels could enhance diagnostic and prognostic interpretations in AD research.
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