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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2023

Open Access 01-12-2023 | Vascular Dementia | Research

Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia

Authors: Xin Ying Chua, Federico Torta, Joyce R. Chong, Narayanaswamy Venketasubramanian, Saima Hilal, Markus R. Wenk, Christopher P. Chen, Thiruma V. Arumugam, Deron R. Herr, Mitchell K. P. Lai

Published in: Alzheimer's Research & Therapy | Issue 1/2023

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Abstract

Background

Alzheimer’s disease (AD) and vascular dementia (VaD) are two of the commonest causes of dementia in the elderly. Of the myriad biomolecules implicated in dementia pathogenesis, sphingolipids have attracted relatively scant research attention despite their known involvement in multiple pathophysiological processes. The potential utility of peripheral sphingolipids as biomarkers in dementia cohorts with high concomitance of cerebrovascular diseases is also unclear.

Methods

Using a lipidomics platform, we performed a case–control study of plasma sphingolipids in a prospectively assessed cohort of 526 participants (non-cognitively impaired, NCI = 93, cognitively impaired = 217, AD = 166, VaD = 50) using a lipidomics platform.

Results

Distinct patterns of sphingolipid alterations were found in AD and VaD, namely an upregulation of d18:1 species in AD compared to downregulation of d16:1 species in VaD. In particular, GM3 d18:1/16:0 and GM3 d18:1/24:1 showed the strongest positive associations with AD. Furthermore, evaluation of sphingolipids panels showed specific combinations with higher sensitivity and specificity for classification of AD (Cer d16:1/24:0. Cer d18:1/16:0, GM3 d16:1/22:0, GM3 d18:1/16:0, SM d16:1/22:0, HexCer d18:1/18:0) and VAD (Cer d16:1/24:0, Cer d18:1/16:0, Hex2Cer d16:1/16:0, HexCer d18:1/18:0, SM d16:1/16:0, SM d16:1/20:0, SM d18:2/22:0) compared to NCI.

Conclusions

AD and VaD are associated with distinct changes of plasma sphingolipids, warranting further studies into underlying pathophysiological mechanisms and assessments of their potential utility as dementia biomarkers and therapeutic targets.
Appendix
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Metadata
Title
Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia
Authors
Xin Ying Chua
Federico Torta
Joyce R. Chong
Narayanaswamy Venketasubramanian
Saima Hilal
Markus R. Wenk
Christopher P. Chen
Thiruma V. Arumugam
Deron R. Herr
Mitchell K. P. Lai
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-023-01359-7

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