The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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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Cutler, R. G., Kelly, J., Storie, K., Pedersen, W. A., Tammara, A., Hatanpaa, K., Troncoso, J. C., & Mattson, M. P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305799101 · Cited by 1,008
Ceramide in apoptosis: an overview and current perspectives
Pettus, B. J., Chalfant, C. E., & Hannun, Y. A. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(02)00331-1 · Cited by 788
Evidence for a membrane defect in Alzheimer disease brain.
Nitsch, R. M., Blusztajn, J. K., Pittas, A. G., Slack, B. E., Growdon, J. H., & Wurtman, R. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.5.1671 · Cited by 536
Deregulation of sphingolipid metabolism in Alzheimer’s disease
He, X., Huang, Y., Li, B., Gong, C.-X., & Schuchman, E. H. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.05.010 · Cited by 516
Characterization of Ceramide Synthase 2
Laviad, E. L., Albee, L. D., Pankova-Kholmyansky, I., Epstein, S., Park, H. J., Merrill, A. H., & Futerman, A. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707386200 · Cited by 476
Hofmann, K., Tomiuk, S., Wolff, G., & Stoffel, W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.11.5895 · Cited by 309
Imgrund, S., Hartmann, D., Farwanah, H., Eckhardt, M., Sandhoff, R., Degen, J., Gieselmann, V., Sandhoff, K., & Willecke, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.031971 · Cited by 299
Roles and regulation of secretory and lysosomal acid sphingomyelinase
Jenkins, R. W., Canals, D., & Hannun, Y. A. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.01.026 · Cited by 286
Katsel, P., Li, C., & Haroutunian, V. H. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9297-x · Cited by 244
Jana, A., Hogan, E. L., & Pahan, K. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.12.010 · Cited by 233
Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells
Mesicek, J., Lee, H., Feldman, T., Jiang, X., Skobeleva, A., Berdyshev, E. V., Haimovitz‐Friedman, A., FUKS, Z. Y., & Kolesnick, R. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.04.006 · Cited by 229
Jennemann, R., Sandhoff, R., Wang, S., Kiss, É., Gretz, N., Zuliani, C., Martín-Villalba, A., Jäger, R., Schorle, H., Kenzelmann, M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500893102 · Cited by 184
Mammalian Neutral Sphingomyelinases: Regulation and Roles in Cell Signaling Responses
Wu, B. X., Clarke, C. J., & Hannun, Y. A. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-010-8120-z · Cited by 151
Sphingolipid metabolism in neural cells
van Echten‐Deckert, G., & Herget, T. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.06.009 · Cited by 144
High activity of acid sphingomyelinase in major depression
Kornhuber, J., Medlin, A., Bleich, S., Jendrossek, V., Henkel, A. W., Wiltfang, J., & Gulbins, E. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0374-5 · Cited by 143
The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids
de la Monte, S. M., Longato, L., Tong, M., DeNucci, S. M., & Wands, J. R. (2009) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph6072055 · Cited by 137
Sphingolipid metabolites in neural signalling and function
Colombaioni, L., & Garcia‐Gil, M. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.07.014 · Cited by 119
Dementia syndromes: evaluation and treatment
Scott, K. R., & Barrett, A. M. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.4.407 · Cited by 113
Kasumov, T., Huang, H., Chung, Y., Zhang, R., McCullough, A. J., & Kirwan, J. P. (2010) · Analytical Biochemistry · doi:10.1016/j.ab.2010.02.023 · Cited by 102
Zimmermann, C., Ginis, I., Furuya, K., Klimanis, D., Ruetzler, C. A., Spatz, M., & Hallenbeck, J. M. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02028-5 · Cited by 92
Marks, N., Berg, M. J., Saito, M., & Saito, M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.10.066 · Cited by 41
Haynes, T.-A. S., Duerksen-Hughes, P. J., Filippova, M., Filippov, V. A., & Zhang, K. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2008.03.045 · Cited by 15
Self-citationZhang, K., Haynes, T.-A. S., Filippova, M., Filippov, V. A., & Duerksen-Hughes, P. J. (2011) · Analytical Methods · doi:10.1039/c1ay05022b · Cited by 10
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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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