Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia
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 mul...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-12-01
|
| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-023-01359-7 |
| _version_ | 1827581779396001792 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Xin Ying Chua |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:41:15Z |
| format | Article |
| id | doaj.art-504a7fb1e0244d43871ae662fd979401 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-03-08T22:41:15Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-504a7fb1e0244d43871ae662fd9794012023-12-17T12:09:08ZengBMCAlzheimer’s Research & Therapy1758-91932023-12-0115111610.1186/s13195-023-01359-7Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementiaXin Ying Chua0Federico Torta1Joyce R. Chong2Narayanaswamy Venketasubramanian3Saima Hilal4Markus R. Wenk5Christopher P. Chen6Thiruma V. Arumugam7Deron R. Herr8Mitchell K. P. Lai9Department of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeSingapore Lipidomics Incubator (SLING), Department of Biochemistry, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeRaffles Neuroscience Centre, Raffles HospitalDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeSingapore Lipidomics Incubator (SLING), Department of Biochemistry, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Cardiovascular Biology and Disease Research, Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe UniversityDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeAbstract 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.https://doi.org/10.1186/s13195-023-01359-7Alzheimer’s diseaseBiomarkersLipidomicsSphingolipidsVascular dementia |
| spellingShingle | 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 Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia Alzheimer’s Research & Therapy Alzheimer’s disease Biomarkers Lipidomics Sphingolipids Vascular dementia |
| title | Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia |
| title_full | Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia |
| title_fullStr | Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia |
| title_full_unstemmed | Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia |
| title_short | Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia |
| title_sort | lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in alzheimer s disease and vascular dementia |
| topic | Alzheimer’s disease Biomarkers Lipidomics Sphingolipids Vascular dementia |
| url | https://doi.org/10.1186/s13195-023-01359-7 |
| work_keys_str_mv | AT xinyingchua lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT federicotorta lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT joycerchong lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT narayanaswamyvenketasubramanian lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT saimahilal lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT markusrwenk lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT christopherpchen lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT thirumavarumugam lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT deronrherr lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia AT mitchellkplai lipidomicsprofilingrevealsdistinctpatternsofplasmasphingolipidalterationsinalzheimersdiseaseandvasculardementia |