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Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis
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.
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“Notably, previous studies have shown that the lipids that were or tended to be decreased in PLCG2 KO mice (cerebrosides, sulfatides and plasmalogens) have been also reported to be decreased early in AD (39–41).”
From Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain (2023) · cites this paper as [39]
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Metadata
- Authors
- Han, X., M. Holtzman, D., W. McKeel, D., Kelley, J., & Morris, J. C.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Han, Xianlin
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2002-08
- Volume
- 82
- Issue
- 4
- Pages
- 809-818
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1594975246
- Cited by
- 626
- References
- 56
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 29 · 2023: 32 · 2022: 32 · 2021: 29 · 2020: 32 · 2019: 22 · 2018: 29 · 2017: 33 · 2016: 34 · 2015: 24 · 2014: 33 · 2013: 33 · 2012: 36
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p41rr000954-34)
- National Institute on Aging (P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991)
- National Center for Research Resources (P41RR00954-240043)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, sulfatide, ceramide, white matter, gray matter, brain lipid composition, pathogenesis
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Brain Chemistry, Ceramides, Dementia, Galactosylceramides, Humans, Neuropsychological Tests, Severity of Illness Index, Sphingomyelins, Sulfoglycosphingolipids, Sulfotransferases, Disease Progression, Spectrometry, Mass, Electrospray Ionization
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