title: Brain lipidomes of subcortical ischemic vascular dementia and mixed dementia.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China; Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Sin Man
authors.initials: SM
authors.lastname: Lam
authors.affiliation: NGS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Life Science Institute, National University of Singapore, Singapore.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore; Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Memory, Aging and Cognition Centre, National University Health System, Singapore.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Memory, Aging and Cognition Centre, National University Health System, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. Electronic address: ghshui@genetics.ac.cn.
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D002908:Chronic Disease; D015140:Dementia, Vascular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D050178:Monoglycerides / Q000032:analysis; D010743:Phospholipids / Q000032:analysis*; D013107:Sphingolipids / Q000032:analysis*; D013433:Sulfoglycosphingolipids / Q000032:analysis; D013702:Temporal Lobe / Q000378:metabolism; D066127:White Matter / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D050178:Monoglycerides; D010743:Phospholipids; D013107:Sphingolipids; D013433:Sulfoglycosphingolipids; C012786:bis(monoacylglyceryl)phosphate
keywords: Alzheimer's disease; Lipidomics; Mass spectrometry; Mixed dementia; Phospholipids; Sphingolipids; Subcortical ischemic vascular dementia