Cited by 264Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchAlzheimer's disease research and treatments

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Increased Ceramide in Brains with Alzheimer's and Other Neurodegenerative Diseases

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Filippov, Valery, Song, Minwoo Andrew, Zhang, Kangling, Vinters, Harry V., Tung, Spencer, Kirsch, Wolff M., Yang, Jun, Duerksen-Hughes, Penelope J.·2012·Journal of Alzheimer s Disease

DOI 10.3233/jad-2011-111202PMC PMC3643694

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Abstract

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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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: Filippov, Valery
Song, Minwoo Andrew
Zhang, Kangling
Vinters, Harry V.
Yang, Jun
Duerksen-Hughes, Penelope J.
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
DOI: 10.3233/jad-2011-111202
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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Increased Ceramide in Brains with Alzheimer's and Other Neurodegenerative Diseases

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