The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia

NEUROBIOLOGY OF AGING

卷:35

Article

Lam, Sin Man^1,2  Wang, Yuting³  Duan, Xinrui⁴  Wenk, Markus R.^2,5  Kalaria, Raj N.⁶  Chen, Christopher P.^7,8  Lai, Mitchell K. P.^7,8  Shui, Guanghou¹ 

[1] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China

[2] Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore

[3] Natl Univ Singapore, NGS Grad Sch Integrat Sci & Engn, Singapore, Singapore

[4] Natl Univ Singapore, Inst Life Sci, Singapore, Singapore

[5] Natl Univ Singapore, Dept Biochem, Singapore, Singapore

[6] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore

[8] Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore, Singapore

关键词: Lipidomics;    Subcortical ischemic vascular dementia;    Mixed dementia;    Alzheimer's disease;    Sphingolipids;    Phospholipids;    Mass spectrometry;   

DOI  :  10.1016/j.neurobiolaging.2014.02.025

来源: Elsevier

【 摘 要 】

Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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