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.