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Increased Ceramide in Brains with Alzheimer's and Other Neurodegenerative Diseases
Open accessAbstract
Ceramide has been suggested to participate in the neuronal cell death that leads to Alzheimer's disease (AD), but its role is not yet well-understood. We compared the levels of six ceramide subspecies, which differ in the length of their fatty acid moieties, in brains from patients who suffered from AD, other neuropathological disorders, or both. We found elevated levels of Cer16, Cer18, Cer20, and Cer24 in brains from patients with any of the tested neural defects. Moreover, ceramide levels were highest in patients with more than one neuropathologic abnormality. Interestingly, the range of values was higher among brains with neural defects than in controls, suggesting that the regulation of ceramide synthesis is normally under tight control, and that this tight control may be lost during neurodegeneration. These changes, however, did not alter the ratio between the tested ceramide species. To explore the mechanisms underlying this dysregulation, we evaluated the expression of four genes connected to ceramide metabolism: ASMase, NSMase 2, GALC, and UGCG. The patterns of gene expression were complex, but overall, ASMase, NSMase 2, and GALC were upregulated in specimens from patients with neuropathologic abnormalities in comparison with age-matched controls. Such findings suggest these genes as attractive candidates both for diagnostic purposes and for intervening in neurodegenerative processes.
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“a process downregulated in AD brains34.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [34]
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“Specifically, increased levels of Cer16, Cer18, Cer20, and Cer24 are found in the brains from patients with AD. 26”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [26]
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“Recent studies show that ceramide is increased in human brains as a function of age (Park et al., 2018) and in Alzheimer’s disease (Filippov et al., 2012), suggesting that a common mechanism could drive age-related early endosome defects in neurons and the RPE.”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Filippov et al., 2012
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Metadata
- Authors
- Filippov, V., Song, M. A., Zhang, K., Vinters, H. V., Tung, S., Kirsch, W. M., Yang, J., & Duerksen-Hughes, P. J.
- Affiliations
- Loma Linda University (US)
- University of California, Los Angeles (US)
- Hangzhou Normal University (CN)
- Corresponding author
- Duerksen-Hughes, Penelope J.
- ORCID
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2012-03-30
- Volume
- 29
- Issue
- 3
- Pages
- 537-547
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3643694
- OpenAlex
- W2145962946
- Cited by
- 264
- References
- 23
- Citations by year
- 2026: 12 · 2025: 28 · 2024: 28 · 2023: 29 · 2022: 27 · 2021: 22 · 2020: 26 · 2019: 11 · 2018: 17 · 2017: 21 · 2016: 14 · 2015: 8 · 2014: 10 · 2013: 10 · 2012: 1
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P50AG016570, P50-AG 16570)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- ceramide, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Ceramides, Chromatography, High Pressure Liquid, Female, Galactosylceramidase, Gene Expression Regulation, Humans, Male, RNA, Messenger, Sphingomyelin Phosphodiesterase, Case-Control Studies, Neurodegenerative Diseases, Tandem Mass Spectrometry
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