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

Chua, XY; Torta, F; Chong, JR; Venketasubramanian, N; Hilal, S; Wenk, MR; Chen, CP; Arumugam, Thiruma; Herr, DR; Lai, MKP

doi:10.26181/24941295.v1

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

journal contribution

posted on 2024-01-04, 05:16 authored by XY Chua, F Torta, JR Chong, N Venketasubramanian, S Hilal, MR Wenk, CP Chen, Thiruma ArumugamThiruma Arumugam, DR Herr, MKP Lai

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.

Funding

This work was supported by grants from the National Medical Research Council of Singapore (MOH-000500–03, MOH-000707–01) and the Healthy Longevity Translational Research Programme of the Yong Loo Lin School of Medicine (HLTRP/2022/PS-01).

History

Publication Date

2023-12-12

Journal

Alzheimer's Research and Therapy

Volume

15

Article Number

214

Pagination

16p.

Publisher

BMC

ISSN

1758-9193

Rights Statement

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