Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease

Potential role in disease pathogenesis

Xianlin Han, David M. Holtzman, Daniel W. McKeel, John Kelley, John C. Morris

Research output: Contribution to journalArticle

378 Citations (Scopus)

Abstract

In addition to pathology in the gray matter, there are also abnormalities in the white matter in Alzheimer's disease (AD). Sulfatide species are a class of myelin-specific sphingolipids and are involved in certain diseases of the central nervous system. To assess whether sulfatide content in gray and white matter in human subjects is associated with both the presence of Alzheimer's disease (AD) pathology as well as the stage of dementia, we analyzed the sulfatide content of brain tissue lipid extracts by electrospray ionization mass spectrometry from 22 subjects whose cognitive status at time of death varied from no dementia to very severe dementia. All subjects with dementia had AD pathology. The results demonstrate that: (i) sulfatides were depleted up to 93% in gray matter and up to 58% in white matter from all examined brain regions from AD subjects with very mild dementia, whereas all other major classes of lipid (except plasmalogen) in these subjects were not altered in comparison to those from age-matched subjects with no dementia; (ii) there was no apparent deficiency in the biosynthesis of sulfatides in very mild AD subjects as characterized by the examination of galactocerebroside sulfotransferase activities in post-mortem brain tissues; (iii) the content of ceramides (a class of potential degradation products of sulfatides) was elevated more than three-fold in white matter and peaked at the stage of very mild dementia. The findings demonstrate that a marked decrease in sulfatides is associated with AD pathology even in subjects with very mild dementia and that these changes may be linked with early events in the pathological process of AD.

Original languageEnglish (US)
Pages (from-to)809-818
Number of pages10
JournalJournal of Neurochemistry
Volume82
Issue number4
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Fingerprint

Sulfoglycosphingolipids
Ceramides
Dementia
Alzheimer Disease
Pathology
Brain
galactosylceramide sulfotransferase
Plasmalogens
Tissue
Lipids
Electrospray ionization
Sphingolipids
Tissue Extracts
Electrospray Ionization Mass Spectrometry
Central Nervous System Diseases
Biosynthesis
Neurology
Pathologic Processes
Myelin Sheath
Mass spectrometry

Keywords

  • Alzheimer's disease
  • Ceramide elevation
  • Galactocerebroside
  • Galactocerebroside sulfotransferase
  • Mass spectrometry
  • Sulfatide deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease : Potential role in disease pathogenesis. / Han, Xianlin; Holtzman, David M.; McKeel, Daniel W.; Kelley, John; Morris, John C.

In: Journal of Neurochemistry, Vol. 82, No. 4, 01.08.2002, p. 809-818.

Research output: Contribution to journalArticle

Han, Xianlin ; Holtzman, David M. ; McKeel, Daniel W. ; Kelley, John ; Morris, John C. / Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease : Potential role in disease pathogenesis. In: Journal of Neurochemistry. 2002 ; Vol. 82, No. 4. pp. 809-818.
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