title: The Association Between Plasma Ceramides and Sphingomyelins and Risk of Alzheimer's Disease Differs by Sex and APOE in the Baltimore Longitudinal Study of Aging.
abstract: BACKGROUND
  Cellular and animal studies demonstrated relationships between sphingolipid metabolism and Alzheimer's disease (AD) pathology. High blood ceramide levels have been shown to predict cognitive impairment and AD, but these studies had small sample sizes and did not assess differences in risk by sex or APOE genotype.
  
  
  OBJECTIVE
  To determine whether plasma ceramides and sphingomyelins were associated with risk of AD, and whether the association varied by sex and APOE genotype.
  
  
  METHODS
  Participants included 626 men and 366 women, aged 55 years and older, enrolled in the Baltimore Longitudinal Study of Aging. Plasma ceramides and sphingomyelins were determined using quantitative analyses performed on a high-performance liquid chromatography coupled electrospray ionization tandem mass spectrometer. Cox proportional hazards models, stratified by sex, were used to examine the relationship of plasma ceramides and sphingomyelins with risk of AD over a mean (SD) follow-up of 15.0 (7.0) years for men and 13.1 (5.9) years for women.
  
  
  RESULTS
  Among men, the highest tertile of most ceramides and sphingomyelins were associated with an increased risk of AD. Among women, there were no associations between any of the ceramides and risk of AD. In contrast, women in the highest tertile of most sphingomyelins had a reduced risk of AD, which was most pronounced among APOE ɛ4 carriers.
  
  
  CONCLUSIONS
  These results provide further evidence for the role of sphingolipid metabolism in AD and highlight the importance of considering sex and APOE genotype in assessing this relationship.
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.|Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Dingfen
authors.initials: D
authors.lastname: Han
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Veera Venkata Ratnam
authors.initials: VVR
authors.lastname: Bandaru
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D002518:Ceramides / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D013109:Sphingomyelins / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D002518:Ceramides; D013109:Sphingomyelins
keywords: Alzheimer’s disease; Epidemiology; ceramides; cohort study; lipids; longitudinal; sex differences