Sin Man Lam, Yuting Wang, Xinrui Duan, Markus R. Wenk, Raj N

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The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia  Sin Man Lam, Yuting Wang, Xinrui Duan, Markus R. Wenk, Raj N. Kalaria, Christopher P. Chen, Mitchell K.P. Lai, Guanghou Shui  Neurobiology of Aging  Volume 35, Issue 10, Pages 2369-2381 (October 2014) DOI: 10.1016/j.neurobiolaging.2014.02.025 Copyright © 2014 The Authors Terms and Conditions

Fig. 1 Changes in the levels of individual lipid subclasses amongst control (n = 14), SIVD (n = 11), and MixD (n = 10) for (A) white matter and (B) gray matter. Lipid classes were expressed as mean molar fractions with error bars indicating mean ± standard errors. Abbreviations: MixD, mixed dementia; SIVD, subcortical ischemic vascular dementia. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 2 Comparative lipid profiles of sphingolipids including (A) Cer, (B) SM, (C) GluCer, (D) GM3, (E) GalCer, and (F) SL in the white matter of control (n = 14), SIVD (n = 11), and MixD (n = 10). Lipid species were expressed as mean molar fractions with error bars indicating mean ± standard errors. Abbreviations: Cer, ceramides; GalCer, galactosylceramides; GM3, ganglioside mannoside 3; GluCer, glucosylceramides; MixD, mixed dementia; SIVD, subcortical ischemic vascular; SL, sulfatides; SM, sphingomyelins. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 3 Heatmaps illustrate the fold change in individual phospholipid species in the white matter of SIVD and MixD compared against control from the subclasses of (A) PC, (B) PG, (C) PS, and (D) PE. Abbreviations: PC, phosphatidylcholines; PE, phosphatidylethanolamines; PG, phosphatidylglycerols; PS, phosphatidylserines. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 4 Comparative lipid profiles of sphingolipids including (A) Cer, (B) SM, (C) GluCer, (D) GM3, (E) GalCer, and (F) SL in the gray matter of control (n = 14), SIVD (n = 11), and MixD (n = 10). Lipid species were expressed as mean molar fractions with error bars indicating mean ± standard errors. Abbreviations: Cer, ceramides; GalCer, galactosylceramides; GM3, ganglioside mannoside 3; GluCer, glucosylceramides; MixD, mixed dementia; SIVD, subcortical ischemic vascular; SL, sulfatides; SM, sphingomyelins. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 5 Heatmaps illustrate the fold change in individual phospholipid species in the gray matter of SIVD and MixD compared against control from the subclasses of (A) PC, (B) PG, (C) Lyso-PC, (D) PA, (E) LBPA, and (F) PE. Abbreviations: LBPA, lysobisphosphatidic acids; MixD, mixed dementia; PA, phosphatidic acids; PC, phosphatidylcholines; PE, phosphatidylethanolamines; PG, phosphatidylglycerols; PS, phosphatidylserines. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 6 Changes in the selected classes of lipids in the gray matter as a function of increasing CERAD plaque score. The levels of (A) specific lipid subclasses and individual species from subclasses of (B) DAG, (C) PS, (D) SM, and (E) PE were significantly perturbed with increasing CERAD. Lipid species were expressed as mean molar fractions with error bars indicating mean ± standard errors. Abbreviations: DAG, diacyglycerides; PE, phosphatidylethanolamines; PS, phosphatidylserines; SM, sphingomyelins. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions

Fig. 7 Summary of the differences in perturbed sphingolipid metabolisms between SIVD white matter and MixD gray matter. While an enhanced shunt of Cer precursors to SM synthesis was observed in SIVD white matter, an increased channeling of Cer for biosynthesis of complex glycosphingolipids downstream was noted in MixD gray matter. Bold arrows indicate increased channeling while dotted arrows indicate reduced channeling. The alterations in sphingolipid levels were subdivided based on fatty acyl chain lengths, with red indicating increase and green indicating reduction. Abbreviations: Cer, ceramides; MixD, mixed dementia; SIVD, subcortical ischemic vascular; SM, sphingomyelins. Neurobiology of Aging 2014 35, 2369-2381DOI: (10.1016/j.neurobiolaging.2014.02.025) Copyright © 2014 The Authors Terms and Conditions